Biomedical subjects

B Schuster

Publications and source records attributed to B Schuster.

At least 37 records · Page 2Linked to original sources

PubMed1995

A comparison of structure and thermal behavior in human plasma lipoprotein(a) and low-density lipoprotein. Calorimetry and small-angle X-ray scattering.

Differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) studies have been performed to investigate the structural properties of lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) obtained from the same donor. In addition, a comparison was made between autologous LDL and the remnant particle Lp(a-) obtained by removal of apo(a) through chemical reduction. With Lp(a), three distinct thermal transitions have been observed: the first one around 20 degrees C, arising from the core-located apolar lipids, similar to LDL but with a significantly lower melting temperature as compared to LDL of the same donor. The second one, at 55.7 +/- 0.25 degrees C, can be attributed to apo(a), since it was found to be absent in Lp(a-) and LDL, whereas isolated apo(a) in aqueous solution exhibited a similar transition. The third transition, at 80.4 +/- 0.9 degrees C, corresponds to apo-B100 protein unfolding. The low melting temperature of the core lipids in Lp(a) is preserved in Lp(a-); this suggests that the apolar lipid interactions are unaffected by apo(a) binding, and that the difference in the core melting behavior between Lp(a) and LDL is due to a different stabilization through interaction between the apolar core and the surface monolayer lipids. SAXS curves exhibited qualitatively the same characteristic features for LDL, Lp(a), and Lp(a-). Thus, the SAXS results showed that no major deviations from spherical particle shape occur with Lp(a), indicating that apo(a) wraps around the particle surface without major globular protrusions into the aqueous surrounding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Pharmacokinetics of an extended-dose halofantrine regimen in patients with malaria and in healthy volunteers.

The pharmacokinetics and tolerance of a 4.5 gm 7-day halofantrine loading dose regimen were evaluated in 10 Thai patients with malaria and in 10 noninfected volunteers. Halofantrine peak plasma concentrations and bioavailability on the first day of treatment were significantly lower in patients with malaria than in healthy volunteers. Halofantrine elimination half-life was significantly shorter in patients with malaria than healthy control subjects (9.5 versus 15.8 days). These data show a distinct effect of acute malaria on the absorption and elimination of the drug. In addition, marked intersubject and intrasubject variability in peak and trough halofantrine levels was observed, indicating variable drug absorption. This dosing regimen was effective and well tolerated, with mild transient diarrhea during the first few days of treatment in both groups. To produce consistently effective drug levels, the currently recommended dosing regimens may be suboptimal. Slow halofantrine elimination raises concern for induction of parasite resistance when the drug is used in endemic areas of the world.

Administration, Oral↗

PubMed1995

[Vestibular lesion in sudden deafness: a prognostic criterium for therapeutic success].

The influence of vestibular dysfunction on severity of initial hearing loss and success of therapy was evaluated in a retrospective study with 142 patients suffering from idiopathic sudden hearing loss. In 48% of these patients combined cochleovestibular disorders were found. In this group mean hearing loss was significantly higher (45 dB versus 32 dB) and hearing recovery after therapy (25% versus 38%) less pronounced. 83% of patients with high grades of vestibular disorders (Vestibular Index: > or = 9) showed a decrease of hearing function between 50 dB and 130 dB compared to 32% in the group with signs of low vestibular dysfunction. Additional vestibular lesion in patients with sudden deafness can be used as a criteria for prognosis. High grade vestibular lesion reduce the probability of complete hearing recovery.

Adolescent↗

PubMed1995

Effect of temperature and phase transition on oxidation resistance of low density lipoprotein.

The study of the effect of temperature on the kinetics of low density lipoprotein (LDL) oxidation was carried out by measuring the conjugated diene (CD) versus time curves at a fixed LDL concentration (0.1 microM) and at different Cu2+ concentrations (0.5-10 microM) in a wide temperature range, from 10 degrees C to 45 degrees C. The core melting point of the LDL determined with differential scanning calorimetry was 31.1 degrees C. We have demonstrated that temperature exerts a clear effect in the Cu(2+)-mediated LDL oxidation, with a strong decrease in lag time and a notable increase in the rate of propagation. This temperature dependence of lag time and rate of propagation fully obeys the Arrhenius law, suggesting that the core melting point of the LDL has no or only a minor effect on these oxidation indices. The Arrhenius plots of the binding of Cu2+ to LDL, measured by K, gave two breaks suggesting that this value is affected by the core transition of the LDL as well as by structural changes at around 15 degrees C. The mean activation energy during rate of initiation was 13.5 kcal/mol and tended to decrease with increasing Cu2+ concentration. The activation energy in the propagation phase was 10.6 kcal/mol and was independent of Cu2+ concentration. In this work we have also shown that the CD method can be conducted with high reproducibility and that a sucrose-supplemented plasma frozen at -80 degrees C can be used as a source of LDL with an unvarying vitamin E content and reproducible oxidation properties.

Blood Preservation↗

PubMed1994

Serine-202 is the putative precursor of the active site dehydroalanine of phenylalanine ammonia lyase. Site-directed mutagenesis studies on the enzyme from parsley (Petroselinum crispum L.).

To investigate the possible role of serine as a precursor of dehydroalanine at the active site of phenylalanine ammonia lyase, two serines, conserved in all known PAL and histidase sequences, were changed to alanine by site-directed mutagenesis. The resulting mutant genes were subcloned into the expression vector pT7.7 and the gene products were assayed for PAL activity. Mutant PALMutS209A showed the same catalytic property as wild-type PAL, whereas mutant PALMutS202A was devoid of catalytic activity, indicating that serine-202 is the most likely precursor of the active site dehydroalanine.

Alanine↗

PubMed1994

Azithromycin prophylaxis against a chloroquine-resistant strain of Plasmodium falciparum.

Azithromycin has antimalarial activity and favourable pharmacokinetic properties for a prophylactic antimalarial agent. We investigated the ability of azithromycin to prevent malaria in volunteers infected with a chloroquine-resistant strain of Plasmodium falciparum. 4 volunteers received oral azithromycin 500 mg followed by 250 mg daily for 7 further days. Subjects were infected on the third day of azithromycin. 3 subjects were protected compared with none of 15 controls. The volunteer not protected by azithromycin had unquantifiable plasma levels of azithromycin, probably because of poor absorption. Azithromycin could be a promising prophylactic agent for P falciparum malaria.

Administration, Oral↗

PubMed1994

Failure of doxycycline as a causal prophylactic agent against Plasmodium falciparum malaria in healthy nonimmune volunteers.

OBJECTIVE: To determine whether doxycycline, 100 mg administered as a single daily oral dose, is effective as a causal prophylactic agent, an agent active against the pre-erythrocytic liver stage of Plasmodium falciparum malaria parasites, in healthy nonimmune persons. If effective, the recommendation by the Centers for Disease Control and Prevention (CDC) that doxycycline be continued for 4 weeks after returning from malaria-endemic areas could be shortened to 1 week. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort Detrick, Maryland. PARTICIPANTS: 18 nonimmune, healthy, adult male volunteers, age 21.7 +/- 2.9 (SD) years, were enrolled in two groups, one of 8 persons and one of 10 persons. Six participants in the first group and 7 in the second group received doxycycline. The remaining participants received placebo. Two volunteers were dropped from the study, leaving 16 participants for analysis. INTERVENTION: Each participant received doxycycline, 100 mg, or placebo in a single daily oral dose starting 3 days before exposure to P. falciparum-infected mosquitoes and ending 6 days after exposure. MEASUREMENTS: Monitoring for parasitemia, plasma doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade. RESULTS: 6 of 6 (100% [95% Cl, 54% to 100%]) participants on doxycycline in the first group and 2 of 6 (33% [Cl, 4% to 78%]) in the second group were protected from malaria. No differences were found between protected and nonprotected participants in the doxycycline elimination half-life (T1/2) (20.8 +/- 5.0 h compared with 21.9 +/- 5.2 h), the steady-state average plasma concentration (1626 +/- 469 ng/mL compared with 1698 +/- 651 ng/mL), or other pharmacokinetic parameter estimates. The mean mosquito salivary-gland sporozoite grade was significantly higher (P = 0.02) in protected (3.5 +/- 0.3) than in nonprotected persons (3.1 +/- 0.1). Overall, 8 of 12 persons on doxycycline were protected from malaria, yielding a causal prophylactic efficacy rate of 67% (Cl, 35% to 90%). CONCLUSIONS: A dosing regimen of doxycycline, 100 mg once daily, administered as a causal prophylactic agent against P. falciparum malaria in healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore, the CDC recommendation that doxycycline should be taken daily starting 1 to 2 days before travel, during travel, and for 4 weeks after travel should still be followed.

Administration, Oral↗

PubMed1994

Efficacy and tolerance of extended-dose halofantrine for drug-resistant falciparum malaria in Thailand.

New treatments for malaria are urgently needed in areas such as Thailand where highly drug-resistant strains of Plasmodium falciparum are prevalent. Mefloquine is rapidly losing efficacy and conventional doses of halofantrine are infective. We therefore used pharmacokinetic stimulation to design an extended-dose halofantrine regimen and tested it in 26 soldiers stationed along the Thai-Cambodian border. Halofantrine was given after meals as three doses of 500 mg each at 4-hr intervals on the first day, followed by 500 mg a day for six days (total dose 4.5 g). Twenty-six soldiers treated with quinine-tetracycline for seven days (Q7T7) served as controls. There were no significant differences in efficacy between halofantrine and Q7T7 (P > 0.1) as assessed by cure rate (92% versus 85%), mean parasite clearance time (82 hr versus 81 hr), or mean fever clearance time (93 hr versus 99 hr). Halofantrine was better tolerated than Q7T7. The side effects score was lower (2 versus 11; P < 0.001), there were less days on which side effects occurred (2.0 days versus 5.5 days; P < 0.001), and fewer patients had adverse effects on every treatment day (4% versus 42%; P < 0.01). High-dose halofantrine is as effective and better tolerated than quinine-tetracycline for multidrug-resistant falciparum malaria.

Adult↗

PubMed1993

The perspectives of current trainees in combined internal medicine-pediatrics. Results of a national survey.

OBJECTIVE: To gather information from combined internal medicine-pediatric residents about their application process for residency, their perceptions of the stressors during residency, and their future plans. DESIGN: Survey of all combined internal medicine-pediatric residents-in-training in the 1989-1990 academic year. PARTICIPANTS: Fifty-four percent of residents-in-training responded to the survey, representing 70% of the programs. RESULTS: Combined residents often investigate and rank other generalist residences. However, internal medicine is significantly (P < .005) considered more often than pediatrics or family medicine. Sixty percent of combined residents do not anticipate further training beyond the 4 years and expect to practice both specialties. The majority of those interested in a subspecialty expect to continue to combine internal medicine and pediatrics in their subspecialty practice. Switching services during the residency engenders stress. Factors that decrease stress include more frequent switches and increasing seniority. Switching from pediatrics to internal medicine is more stressful (P < .0001) than switching to pediatrics from internal medicine. The residents considered ambulatory training sites and a specific coordinator for the program to be the most important features of the residency. CONCLUSIONS: Combined internal medicine-pediatric programs continue to attract a small cohort of well-qualified US medical school graduates, the majority of whom intend to practice as generalists in both pediatrics and internal medicine.

Adult↗

PubMed1993

Tolerability of prophylactic Lariam regimens.

Three hundred and fifty-nine US Marines participated in a randomized double-blind clinical trial to assess tolerance of two prophylactic mefloquine regimens [250 mg salt weekly (n = 157) or 250 mg daily for 3 days followed by 250 mg weekly (n = 46)] compared with 300 mg weekly chloroquine (n = 156) over a 12-week period. The study participants were seen daily for four days, then weekly for 11 weeks. On each visit, the subject answered two computerized questionnaires (a review of body systems and an evaluation of mood states), participated in a physician interview, and was administered medications under supervision. A random sample of each group was assigned to either pharmacokinetic sampling or two wear a wrist watch size computerized sleep monitor (actigraph). The frequencies of intercurrent illness and other concomitant medications were tabulated. End study mefloquine plasma levels were obtained on all study participants. The results obtained showed no compromise in function due to dizziness or incoordination in the mefloquine groups. Overall, both weekly mefloquine and loading dose mefloquine were well tolerated. Sleep disturbance and increased dream activity were detected in the mefloquine groups. Depressive feelings were noted in two to three times more individuals in the mefloquine groups than in the chloroquine group early in the course of the study, and resolved in the majority of subjects as tolerance developed. Steady state mefloquine plasma levels were attained rapidly with the loading dose regimen in four days versus seven weeks with weekly mefloquine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Sulfite-containing Canadian pharmaceutical products available in 1991.

OBJECTIVE: To compile an inclusive list of Canadian pharmaceutical products available in 1991 that contained sulfites. DATA SOURCES: Written and oral responses from 94 pharmaceutical companies selected from the 1989 Compendium of Pharmaceuticals and Specialties. RESULTS: A list of sulfite-containing pharmaceutical products was compiled from data supplied by the 90 responding companies. Companies whose products contained no sulfites were separately identified. CONCLUSIONS: Sulfites are present in many pharmaceutical products and are one of many excipients and additives that have been reported to cause severe adverse reactions. The provided list should be a useful aid for health care practitioners when prescribing pharmaceutical products for sulfite-sensitive patients.

Canada↗

PubMed1992

Paranasal sinusitis associated with nasotracheal and orotracheal long-term intubation.

The impact of nasotracheal and orotracheal long-term intubation on the development of sinusitis paranasalis was investigated in a prospective study. Daily A-scan ultrasound examinations of the maxillary sinuses were performed on 44 intensive care unit patients (20 nasally, 24 orally intubated) who required prolonged intubation (greater than 24 hours). At the end of the investigation period 19 (95%) of 20 nasotracheally and 15 (63%) of 24 orotracheally intubated patients showed pathologic antral sinus findings. In nasally intubated patients the incidence of bilateral sinusitis was significantly higher and its onset sooner. Pathologic organisms were found in the sinus aspirates in seven of 13 nasotracheally intubated patients, but only in two of nine patients with an oral tube. Thus, the nasotracheal tube can be seen as an adding factor in the development of sinusitis paranasalis.

Adult↗

PubMed1992

Long-term weight control study. I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo.

To investigate the value of anorexiant medications as an adjunct to other forms of weight control therapy, we studied 121 people in a 34-week, double-blind clinical trial of 60 mg extended-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise. Participants weighed 130% to 180% (154% +/- 1.2%, mean +/- SEM) of ideal body weight (1983 Metropolitan Life tables) and were in good health. By week 34, participants receiving active medication lost an average of 14.2 +/- 0.9 kg, or 15.9% +/- 0.9% of initial weight (n = 58), versus a loss of 4.6 +/- 0.8 kg or 4.9% +/- 0.9% of initial weight by subjects taking placebo (n = 54; p less than 0.001). On visual analog scales, participants rated fenfluramine plus phentermine as more helpful than placebo (50.3 +/- 0.5 versus 20.3 +/- 0.3) and not bothersome (fenfluramine plus phentermine, 17.4 +/- 0.3 versus 13.5 +/- 0.2). Blood pressure decreased and pulse remained unchanged in both groups. Dry mouth was the most common adverse effect in subjects receiving fenfluramine plus phentermine; all adverse effects decreased after 4 weeks. Only nine participants left the study in the first 34 weeks. Two subjects from each group left the study as a result of adverse effects. Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise aided weight loss and continued to be efficacious for 34 weeks.

Adult↗

PubMed1992

Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise.

Between weeks 34 and 104, we explored different schema for administering fenfluramine plus phentermine in open-label fashion. At week 34, the original placebo group participants began taking fenfluramine plus phentermine (placebo-to-active group). Those receiving fenfluramine plus phentermine between weeks 6 and 34 either continued to receive medication or began targeted intermittent therapy. Participants who did not lose 10% of initial weight received an augmented dose (60 mg fenfluramine plus 30 mg phentermine. The placebo-to-active group lost an additional 9.1 +/- 0.8 kg (mean +/- SEM) in the period from week 34 to week 60. At week 60, they were assigned to either continue medication, intermittent therapy, or augmented therapy. More than 68% (83) of the original participants completed up to study week 104. At that point, overall weight loss was 10.8 +/- 0.7 kg (11.6 +/- 0.8% of initial weight); participants who continued to receive fenfluramine plus phentermine lost 11.6 +/- 0.8 kg, participants receiving intermittent therapy lost 11.6 +/- 1.3 kg, and participants receiving augmented therapy lost 6.5 +/- 1.5 kg. Although 41% of the participants complained of dry mouth, neither serious adverse effects nor evidence of medication abuse appeared. There were 29 dropouts in the period from weeks 34 to 104. Sixteen of those were related to medication (adverse effects, lack of efficacy, and fear of medication). Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise continued to be efficacious for up to 2 years.

Adult↗

PubMed1992

Long-term weight control study. III (weeks 104 to 156). An open-label study of dose adjustment of fenfluramine and phentermine.

Between weeks 104 and 156 we attempted to optimize response by adjusting the doses of fenfluramine and phentermine. Dosing changes were based on an algorithm that aimed to achieve 120% of ideal body weight (IBW) while minimizing adverse effects. The dose groups were as follows: stage I, 30 mg fenfluramine plus 15 mg phentermine in the morning; stage II--continuous or targeted intermittent, 60 mg fenfluramine plus 15 mg phentermine in the morning; stage III, 60 mg fenfluramine plus 30 mg phentermine in the morning; stage IV, 60 mg fenfluramine plus 30 mg phentermine in the morning and 30 mg fenfluramine in the evening; and stage V, 60 mg fenfluramine plus 30 mg phentermine in the morning and 60 mg fenfluramine in the evening. Seventy-seven participants began this segment of the study and 59 completed to week 156. Completers of this segment of the study gained an average of 2.7 +/- 0.5 kg between weeks 104 and 156 but remained 9.4 +/- 0.8 kg (10.5%) below baseline. On average, weight loss from baseline by group was as follows: for stage I (n = 2), 14.1 +/- 6.8 kg; for stage II continuous (n = 14), 10.9 +/- 0.7 kg; for stage II targeted intermittent (n = 7), 8.8 +/- 2.4 kg; for stage III (n = 9), 7.7 +/- 2.6 kg; for stage IV (n = 8), 10.5 +/- 2.6 kg; and for stage V (n = 19), 8.4 +/- 2.4 kg. Upward dose adjustment (n = 36) resulted in further weight loss in 11 and no gain in six participants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Long-term weight control study. IV (weeks 156 to 190). The second double-blind phase.

To assess continued efficacy of anorexiants after 3 years of use, 52 participants (43% of those starting) entered a second double-blind trial to compare 60 mg sustained-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise. Although participants in both the active medication and placebo groups gained weight, participants receiving fenfluramine plus phentermine (n = 27) gained significantly (p less than 0.01) less (4.4 +/- 0.5 kg or 5.3% +/- 0.5% of initial weight) than participants receiving placebo (n = 24) (6.9 +/- 0.8 kg or 8.5% +/- 1.1% of initial weight). At week 190, both groups were still below their initial weight (fenfluramine plus phentermine group, 5.0 +/- 1.4 kg; placebo group, 2.1 +/- 1.2 kg; p less than 0.01). Overall, 12 participants (23.5% of those still in the study) were greater than or equal to 10% below initial weight. One participant dropped out during this phase because of personal reasons and loss of medication efficacy. During the 30 weeks, participants receiving fenfluramine plus phentermine had 26 moderate or severe complaints versus eight participants receiving placebo. Fenfluramine plus phentermine provided better appetite control and only slightly more bother. Analysis of participant response in this phase by treatment assignment in the first double-blind phase (weeks 6 to 34) indicated that initial receipt of medication did not have negative learning effects. Eleven participants receiving active medication between weeks 6 and 34 and receiving placebo between weeks 160 to 190 gained 5.1 +/- 1.0 kg. In contrast, 13 participants originally taking placebo gained 8.3 +/- 9 kg in this second double-blind phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Long-term weight control study. V (weeks 190 to 210). Follow-up of participants after cessation of medication.

Participants who completed up to week 190 in the long-term weight control study were monitored after cessation of medication between weeks 190 and 210. Caloric restriction, behavior modification sessions, exercise reinforcement, and physician visits continued. We assessed whether or not participants had reset their weight control mechanisms and compared the effect of stopping medication under open-label conditions (weeks 190 to 210) with the results of stopping anorexiants under double-blind conditions (weeks 160 to 190). At week 210, participants were, on average, 1.4 +/- 1.0 kg (mean +/- SEM, 1.5% +/- 1.1%) below their weights at baseline (week 0). Of the 48 participants who remained in the study, 13 were still 5% or more and seven were 10% or more below their initial weights. On average, participants gained 2.7 +/- 0.5 kg (3.2%) in the period from weeks 190 to 210. Those who had been taking medication in the period from weeks 160 to 190 gained weight at a somewhat faster rate than those who had been taking placebo. However, participants who had transferred from fenfluramine plus phentermine to no medication in this phase gained at a slower rate than participants who had changed from fenfluramine plus phentermine to placebo under double-blind conditions at week 160 (0.195 kg per week versus 0.277 kg per week). The findings indicate that participants had difficulty maintaining weight loss without anorexiant medications. Despite long periods of time at weights much lower than baseline, permanent resetting of weight control mechanisms could not be shown for most participants.

Adult↗

PubMed1992

Long-term weight control study. VII (weeks 0 to 210). Serum lipid changes.

We analyzed serum total cholesterol, triglycerides, and lipoprotein profile changes occurring in the participants (N = 121) through 210 weeks of the study. On average, baseline lipid levels were within normal limits. The most consistent changes occurred in the high-density lipoprotein cholesterol (HDL-C), serum total cholesterol/HDL-C ratios, and triglyceride levels. HDL-C increased significantly (p less than 0.01), compared with baseline, by 10% at week 34, 15% at week 54, 19% at week 104, and 27% at week 139. At week 210, 20 weeks after treatment had ended, HDL-C was 15% higher than baseline. At weeks 34, 54, 104, and 139, the serum total cholesterol/HDL-C ratio was significantly decreased, compared with baseline, by 9%, 19%, 17%, and 25%, respectively. At week 210, serum total cholesterol/HDL-C ratio was 8% less than week 0. Compared with baseline, triglyceride levels decreased significantly by 21%, 31%, 29%, and 29% at weeks 34, 54, 104, and 139, respectively. At week 210, triglyceride levels were 16% below baseline. Total cholesterol levels and low-density lipoprotein cholesterol (LDL-C) showed less dramatic changes. Patterns of lipid and lipoprotein changes were qualitatively similar between men and women. However, greater decreases in serum total cholesterol, LDL-C, and triglyceride levels were observed in participants with high (n = 10) compared with low (n = 10) baseline lipid levels. Cholesterol changes were not affected by anorexiant medications. However, triglyceride levels at week 34 were significantly (p less than 0.025) less in the participants treated with anorexiants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗