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Biomedical subjects

W Schaffner

Publications and source records attributed to W Schaffner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial.

This study assessed the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared with placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessments by both patients and investigators. A total of 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between the active treatment and the placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from the baseline level after 2 weeks of active treatment, compared with an increase of 2% in the placebo group. The patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of the willow bark extract over the placebo (patients' assessment, p = 0.0002; investigators' assessment, p = 0.0073). It is concluded that the willow bark extract showed a moderate analgesic effect in osteoarthritis and appeared to be well tolerated.

Adult↗
PubMed2001

Influenza vaccine: issues and opportunities.

Several recent developments offer opportunities to improve the diagnosis, treatment, and prevention of influenza. Rapid diagnostic tests assist in selecting patients for antiviral therapy and avoid some antibiotic use. The neuraminidase inhibitors now offer therapeutic options with potentially fewer side effects than the traditional drugs, albeit at greater cost. Inactivated influenza vaccine is now recommended annually for all persons aged 50 and older and younger adults and children (aged 6 months and older) who have underlying risk factors for the severe complications of influenza. This includes pregnant women who are in their second or third trimesters during influenza season.

Adult↗
PubMed2001

Mixed outbreak of parainfluenza type 1 and influenza B associated with tourism and air travel.

BACKGROUND: A preseasonal outbreak of influenza-like illness was reported in a tourist group that had returned from Ireland to the United States on October 1 and 2, 1999. The authors investigated to determine the timing, extent, and nature of the outbreak. METHODS: A cohort study was conducted among the entire group. Cases were defined as illness occurring among tour members who experienced cough or sore throat with onset from September 29 through October 5. Nasopharyngeal and throat cultures were examined for respiratory viruses. RESULTS: Eighteen (60%) of the 30 tourists were ill; the majority (66%) of cases had onset of illness within 1 day of departure from Ireland. Human parainfluenza virus type 1 was isolated from six cultures, and influenza B from three. The attack rate was 100% among the eight persons 65 years of age or older versus 45% among the 22 persons younger than 65 years (P = 0.01). CONCLUSION: International travellers, particularly older persons and members of organized tour groups, may experience increased risks for respiratory viral infection. The recognition and containment of imported infectious diseases depend on prompt reporting and epidemiologic investigation.

Aged↗
PubMed2001

Molecular markers as a tool to verify sexual and apomictic off-spring of intraspecific crosses in Hypericum perforatum.

The aim of this project was to establish RAPD markers to determine the percentage of sexual off-spring of the facultative apomictic plant species H. perforatum. We did reciprocal crosses between four different accessions (A x B, B x A, C x D, D x C) by mechanical emasculation and hand pollination. Genomic DNA of the parents and the off-spring was isolated and PCR conditions were optimized in order to obtain reproducible bands with RAPD markers. Of the 260 screened RAPD primers 127 revealed polymorphism between the parental lines of A and B, whereas 53 revealed no amplification products. Each progeny was tested for the presence of paternal bands with three primers. We found no sexual off-spring among the 22 progenies of A x B, the nine progenies of B x A and the ten progenies of D x C. However, we detected six sexual off-spring among the 45 progenies of C x D. We have proved that RAPD markers can be used to distinguish between sexual and apomictic off-spring in H. perforatum and that sexual off-spring can be obtained from intraspecific crosses. The percentage of sexual progeny might depend on the genotype of the parental lines.

Base Sequence↗
PubMed2001

Interaction of various Piper methysticum cultivars with CNS receptors in vitro.

Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum Forst.) cultivars, Mahakea, Nene, Purple Moi and PNG, were tested on binding affinities to CNS receptors including GABAA (GABA and benzodiazepine binding site), dopamine D2, opioid (mu and delta), serotonin (5-HT6 and 5-HT7) and histamine (H1 and H2). HPLC analysis was carried out in order to determine the amount of the main kavalactones kavain, 7,8-dihydrokavain, methysticin, 7,8-dihydromethysticin, yangonin and 5,6-demethoxyyangonin. The most potent binding inhibition was observed for leaf extracts to GABAA receptors (GABA binding site) with IC50 values of approximately 3 micrograms/ml, whereas root extracts were less active with IC50 values ranging from 5 micrograms/ml (Nene) to 87 micrograms/ml (Mahakea). Since the leaf extracts generally contained lower amounts of the kavalactones than the root extracts, there might exist additional substances responsible for these activities. Leaf extracts also inhibited binding to dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors more potently than the corresponding root extracts with IC50 values ranging from 1 to 100 micrograms/ml vs. > or = 100 micrograms/l, respectively. Significant differences in the potential of binding inhibition were also observed between cultivars. Binding to serotonin (5-HT6 and 5-HT7) and benzodiazepine receptors was only weakly inhibited by both root and leaf extracts of all four cultivars. In conclusion, our investigation indicates that the GABAA, dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors might be involved in the pharmacological action of kava extracts. Since the cultivars contained similar amounts of kavalactones, while their pharmacological activities differed markedly, other constituents may play a role in the observed activities. Additionally, leaves generally exhibited more potent binding inhibition than roots, therefore leaf of P. methysticum might be an interesting subject for further pharmacological studies.

Animals↗
PubMed2001

Neurochemical studies with St. John's wort in vitro.

The effect of extracts and constituents of St. John's wort, Hypericum perforatum, at various CNS receptors were studied by radioligand binding techniques in order to determine a profile of pharmacological activity in vitro. Binding inhibition was examined for the G-protein coupled opioid, serotonin (5-HT), histamine, neurokinin and corticotropin releasing factor (CRF) receptors, for the steroid estrogen-alpha receptor and for the ligand-gated ionchannel GABA(A) receptor. Hypericin showed the most potent binding inhibiton of all tested constituents to human CRF1 receptor with an IC50 value of 300 nM. Preliminary GTPgamma35S binding studies to CRF1 coupled G-protein indicated an antagonistic action for hypericin. The acylphloroglucinole hyperforin failed to inhibit 125I-astressin binding to hCRF, receptor up to 10 microM. Hyperforin inhibited binding to opioid and serotonin (5-HT) receptors at IC50 values between 0.4 and 3 microM, while hypericin and pseudohypericin inhibited with weaker potency. The biflavonoid I3,II8-biapigenin inhibited 3H-estradiol binding to the estrogen-alpha receptor with an IC50 value of 1 microM. The inhibition of 3H-muscimol binding to the GABA(A) receptor is likely to be exclusively due to GABA present in the extract. We therefore hypothesize that additive or synergistic actions of several ditsinct compounds may be responsible for the beneficial antidepressant effect of St. John's wort.

Animals↗
PubMed2001

The Drosophila homolog of mammalian zinc finger factor MTF-1 activates transcription in response to heavy metals.

Metallothioneins (MTs) are short, cysteine-rich proteins for heavy metal homeostasis and detoxification; they bind a variety of heavy metals and also act as radical scavengers. Transcription of mammalian MT genes is activated by heavy metal load via the metal-responsive transcription factor 1 (MTF-1), an essential zinc finger protein whose elimination in mice leads to embryonic lethality due to liver decay. Here we characterize the Drosophila homolog of vertebrate MTF-1 (dMTF-1), a 791-amino-acid protein which is most similar to its mammalian counterpart in the DNA-binding zinc finger region. Like mammalian MTF-1, dMTF-1 binds to conserved metal-responsive promoter elements (MREs) and requires zinc for DNA binding, yet some aspects of heavy metal regulation have also been subject to divergent evolution between Drosophila and mammals. dMTF-1, unlike mammalian MTF-1, is resistant to low pH (6 to 6.5). Furthermore, mammalian MT genes are activated best by zinc and cadmium, whereas in Drosophila cells, cadmium and copper are more potent inducers than zinc. The latter species difference is most likely due to aspects of heavy metal metabolism other than MTF-1, since in transfected mammalian cells, dMTF-1 responds to zinc like mammalian MTF-1. Heavy metal induction of both Drosophila MTs is abolished by double-stranded RNA interference: small amounts of cotransfected double-stranded RNA of dMTF-1 but not of unrelated control RNA inhibit the response to both the endogenous dMTF-1 and transfected dMTF-1. These data underline an important role for dMTF-1 in MT gene regulation and thus heavy metal homeostasis.

Amino Acid Sequence↗
PubMed2000

Vancomycin-resistant enterococci among chronic hemodialysis patients: a prospective study of acquisition.

To determine the prevalence and rate of acquisition of vancomycin-resistant enterococci (VRE) among patients undergoing chronic (i.e., long-term) hemodialysis who were admitted to a tertiary care center, serial rectal cultures for VRE were performed at hospital admission and every 5 days until hospital discharge. A total of 7 (6%) of the 119 patients were colonized with VRE at admission. Six (19%) of the 32 patients who remained in the hospital > or =4 days acquired VRE. A nonambulatory status was significantly associated with colonization at admission (OR, 9.7; 95% CI, 1.8-53; P=.01), and vancomycin exposure was significantly associated with VRE acquisition (relative risk, 1.8; 95% CI, 1.1-2.9; P=.02). All patients acquired VRE from epidemiologically linked dialysis patients colonized with similar VRE genotypes. Hospital acquisition of VRE contributes substantially to the increasing prevalence of VRE in the chronic hemodialysis patient population.

Adult↗
PubMed2000

Mass psychogenic illness attributed to toxic exposure at a high school.

BACKGROUND AND METHODS: Mass psychogenic illness may be difficult to differentiate from illness caused by bioterrorism, rapidly spreading infection, or toxic substances. We investigated symptoms attributed to exposure to toxic gas at a high school in Tennessee. In November 1998, a teacher noticed a 'gasoline-like' smell in her classroom, and soon thereafter she had a headache, nausea, shortness of breath, and dizziness. The school was evacuated, and 80 students and 19 staff members went to the emergency room at the local hospital; 38 persons were hospitalized overnight. Five days later, after the school had reopened, another 71 persons went to the emergency room. An extensive investigation was performed by several government agencies. RESULTS: We were unable to find a medical or environmental explanation for the reported illnesses. The persons who reported symptoms on the first day came from 36 classrooms scattered throughout the school. The most frequent symptoms (in this group and the group of people who reported symptoms five days later) were headache, dizziness, nausea, and drowsiness. Blood and urine specimens showed no evidence of carbon monoxide, volatile organic compounds, pesticides, polychlorinated biphenyls, paraquat, or mercury. There was no evidence of toxic compounds in the environment. A questionnaire administered a month later showed that the reported symptoms were significantly associated with female sex, seeing another ill person, knowing that a classmate was ill, and reporting an unusual odor at the school. CONCLUSIONS: The illness attributed to toxic exposure had features of mass psychogenic illness - notably, widespread subjective symptoms thought to be associated with environmental exposure to a toxic substance in the absence of objective evidence of an environmental cause. Alleviation of the anxiety surrounding an episode of mass psychogenic illness requires prompt recognition and a detailed investigation.

Disease Outbreaks↗
PubMed2000

[Effectiveness and tolerance of standardized willow bark extract in arthrosis patients. Randomized, placebo controlled double-blind study].

OBJECTIVE: To assess the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. METHODS: Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared to placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessment by both patients and investigators. RESULTS: 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between active treatment and placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from baseline level after two weeks of active treatment, compared to an increase of 2% in the placebo group. Patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of willow bark extract over placebo (patients assessment, p = 0.0002; investigators assessment, p = 0.0073). CONCLUSION: Willow bark extract shows a moderate analgesic effect in osteoarthritis.

Activities of Daily Living↗
PubMed2000

Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS).

In a prospective, multicentre trial the efficacy of an Vitex agnus castus L extract Ze 440 was investigated in 50 patients with pre-menstrual syndrome (PMS). The patients were treated daily with one tablet (20 mg native extract) during three menstrual cycles. 43 patients completed the study protocol which encompassed 8 menstrual cycles (2 baseline, 3 treatment and 3 post-treatment). 13/43 patients were receiving concomitant oral contraceptives. 6 patients did not complete the study for reasons not related to study medication, and one patient complained of fatigue possibly related to study medication. All evaluated patients took at least 85% of the prescribed medication. The main effect parameter was the validated Moos' menstrual distress questionnaire (MMDQ), and secondary parameters were a visual analogue scale (VAS; self-assessment) and a global impression scale (GI, self-assessment). The study population was homogenous in age (31.3+/-7.7 years) weight (58.9+/-6.9 kg) and cycle length (28.4+/-0.3 d). The diagnosis was according to DMS-III. At the end of the study, PMS-related symptoms were reduced by treatment. There was a significant score reduction (42.5%) of the MMDQ as the main effect parameter (p<0.001). Symptoms gradually returned after treatment cessation. However, a difference from baseline remained (20%; p<0.001) up to 3 cycles thereafter. 20/43 patients were considered "responders", with a reduction in MMDQ score by at least 50% relative to baseline. At baseline, the VAS score was elevated in the late luteal phase and low at the follicular phase, as expected. During treatment, VAS score decreased in the late luteal phase (47.2%; p<0.01) and remained 21.7% (p<0.001) below baseline after 3 cycles post-cessation of treatment. The low VAS score within the follicular phase remained unchanged over the whole observation period. 38 patients judged the global efficacy moderate to excellent, 5 patients indicated no global efficacy. The number of days patients sustained PMS symptoms was reduced slightly from 7.5 to 6. Resting levels of blood prolactin remained within the physiological range throughout. No differences were seen between patients on or off oral contraceptives. 20 patients reported 37 adverse events (AE). No serious AE were reported. One patint withdrew after four days of treatment due to fatigue and headache. Laboratory safety control parameters were not affected. In conclusion, patients with PMS can be treated successfully with Vitex agnus-castus extract Ze 440, as indicated by clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.

Adult↗
PubMed2000

Hospital-acquired infections among chronic hemodialysis patients.

The epidemiological characteristics of nosocomial infections among patients requiring chronic hemodialysis, a high-risk and rapidly growing population, have not been fully elucidated. During a 30-month cohort study, rates of bloodstream infections (BSIs), urinary tract infections (UTIs), pneumonia, and diarrhea caused by Clostridium difficile and the distribution of pathogens among hospitalized chronic hemodialysis patients were compared with hospitalized patients not requiring chronic hemodialysis. To identify risk factors for developing a nosocomial infection among chronic hemodialysis patients, a matched case-control study was performed. A total of 1,557 nosocomial infections were detected during 1,317 of 68,361 admissions (2%). Of these, 47 nosocomial infections occurred in chronic hemodialysis patients during 31 of 578 admissions (5%). Nosocomial infections were significantly more frequent among the chronic hemodialysis group (9.1/1,000 patient-days) compared with the non-chronic hemodialysis group (3. 8/1,000 patient-days; relative risk [RR], 2.4; 95% confidence interval [CI], 1.8 to 3.2; P < 0.001). UTIs were the most common nosocomial infections among chronic hemodialysis patients, accounting for 47% of all infections in this population. UTIs were significantly more common among chronic hemodialysis patients (4.2/1, 000 patient-days) compared with non-chronic hemodialysis patients (0.7/1,000 patient-days; RR, 6.2; 95% CI, 3.8 to 9.5; P < 0.001). Among chronic hemodialysis patients, Candida spp and enterococci were the most common pathogens in contrast to coagulase-negative staphylococci and Staphylococcus aureus among patients not requiring hemodialysis. Using conditional logistic regression, a greater index of comorbidity was significantly associated with nosocomial infections among the chronic hemodialysis population (odds ratio, 3. 6; 95% CI, 1.2 to 10.7; P = 0.02). Chronic hemodialysis patients are at a substantially greater risk for developing a nosocomial infection compared with other hospitalized patients.

Bacteremia↗
PubMed2000

Vancomycin prescribing practices in hospitalized chronic hemodialysis patients.

To determine the prevalence of and indications for vancomycin administration among hospitalized chronic hemodialysis patients, we performed a 3-month prospective cohort study at a tertiary care center. Modified guidelines for vancomycin use from the Hospital Infections Control Practices Advisory Committee of the Centers for Disease Control and Prevention were used. Vancomycin was administered during 56 of 144 admissions (39%) requiring chronic hemodialysis compared with 336 of 7,212 admissions (5%) not requiring hemodialysis (relative risk, 11; 95% confidence interval, 8 to 15; P < 0.001). Among chronic hemodialysis patients, vancomycin use was judged appropriate for 131 of the 164 vancomycin doses (80%). The most common appropriate indication was empiric therapy in a febrile patient before culture or susceptibility results. Of 32 infections identified in patients who received empiric vancomycin, 15 infections (47%) were caused by beta-lactam-resistant pathogens. Among the 33 doses (20%) judged inappropriate, continued therapy for a presumed infection despite failure to identify a beta-lactam-resistant pathogen was the most common indication. Although vancomycin administration was frequent among hospitalized chronic hemodialysis patients, its use was justified in the majority of cases. Efforts should focus on limiting vancomycin administration for treating infections caused by beta-lactam-sensitive pathogens.

Adult↗
PubMed2000

Pharmacological activities of Vitex agnus-castus extracts in vitro.

The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

Animals↗
PubMed2000

Serological survey and active surveillance for La Crosse virus infections among children in Tennessee.

In 1998 and 1999, we performed a serosurvey and active surveillance for La Crosse encephalitis at a children's hospital in eastern Tennessee. Fifteen cases of La Crosse encephalitis were confirmed. Only 5 (0.5%) of 1000 serum samples being tested at the state laboratory for other diseases had evidence of antibodies to La Crosse virus. These findings suggest that La Crosse virus is newly endemic to eastern Tennessee.

Adolescent↗
PubMed2000

An outbreak of Acinetobacter baumannii: the importance of cross-transmission.

OBJECTIVE: To investigate an outbreak of nosocomial infections due to multidrug-resistant (MDR) Acinetobacter baumannii and to analyze the contribution of cross-transmission in the rise in infection rates. DESIGN: Epidemiological investigation; molecular typing using pulsed-field gel electrophoresis (PFGE); matched case-control study to identify risk factors for infection. SETTING: A 34-bed surgical intensive care unit at a tertiary-care hospital. PATIENTS: Eighteen patients who developed MDRA baumannii nosocomial infection were matched to 36 patients who were admitted to the same surgical intensive care unit (SICU) room and did not develop an infection during the outbreak period. RESULTS: Prior to the outbreak, the baseline attack rate of MDR A baumannii nosocomial infections was 3 per 100 patients per month. From February 1 through March 22, 1998, the attack rate rose to 16 per 100 patients per month, with a total of 18 infections. All isolates had indistinguishable PFGE patterns. Seventy environmental cultures were negative for MDR A baumannii. Following intense infection control education, the attack rate decreased to 4 per 100 patients per month. By conditional logistic regression, cases were exposed to a significantly higher number of patients with MDR A baumannii infections compared to controls (odds ratio, 1.1; 95% confidence interval, 1.01-1.2; P=.02), even after adjusting for length of SICU admission and exposure to antibiotics and invasive devices. CONCLUSION: Cross-transmission between patients contributed to the rise in rates of MDRA baumannii infections. A common environmental source was not detected.

Acinetobacter↗
PubMed2000

Conservation of glutamine-rich transactivation function between yeast and humans.

Several eukaryotic transcription factors such as Sp1 or Oct1 contain glutamine-rich domains that mediate transcriptional activation. In human cells, promoter-proximally bound glutamine-rich activation domains activate transcription poorly in the absence of acidic type activators bound at distal enhancers, but synergistically stimulate transcription with these remote activators. Glutamine-rich activation domains were previously reported to also function in the fission yeast Schizosaccharomyces pombe but not in the budding yeast Saccharomyces cerevisiae, suggesting that budding yeast lacks this pathway of transcriptional activation. The strong interaction of an Sp1 glutamine-rich domain with the general transcription factor TAF(II)110 (TAF(II)130), and the absence of any obvious TAF(II)110 homologue in the budding yeast genome, seemed to confirm this notion. We reinvestigated the phenomenon by reconstituting in the budding yeast an enhancer-promoter architecture that is prevalent in higher eukaryotes but less common in yeast. Under these conditions, we observed that glutamine-rich activation domains derived from both mammalian and yeast transcription factors activated only poorly on their own but strongly synergized with acidic activators bound at the remote enhancer position. The level of activation by the glutamine-rich activation domains of Sp1 and Oct1 in combination with a remote enhancer was similar in yeast and human cells. We also found that mutations in a glutamine-rich domain had similar phenotypes in budding yeast and human cells. Our results show that glutamine-rich activation domains behave very similarly in yeast and mammals and that their activity in budding yeast does not depend on the presence of a TAF(II)110 homologue.

Amino Acid Sequence↗