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Biomedical subjects

R Weber

Publications and source records attributed to R Weber.

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

Long-term evaluation of T-cell subset changes after effective combination antiretroviral therapy during asymptomatic HIV-infection.

Demonstration of long-lived HIV-reservoirs resistant to the effects of combination antiretroviral therapy raises concern over the ability of treatment to maintain long-term beneficial alterations in T-cell subset composition. To address this issue, we have examined the effect of antiretroviral therapy on T-cell subset change during early HIV-infection in a 2-year prospective open-label trial composed of treatment-naive asymptomatic HIV-infected patients with CD4+ T-cell counts > or =400 cells/microl. Therapy consisted of double (zidovudine and lamivudine) or triple (zidovudine, lamivudine, and ritonavir) combination antiretroviral therapy. Retrospective analysis based on magnitude of viral suppression was used to characterize responder and nonresponder groups. Among responders, long-term antiretroviral therapy maintained a significant increase in numbers of total CD4+, naive CD4+/CD45RA+, and memory CD4+/CD45RO+ T cells. A concomitant significant decrease in numbers of memory CD8+/CD45RO+ and both activated CD8+/HLA-DR+ and CD8+/CD38+ T cells was also maintained. In contrast, long-term antiretroviral therapy among nonresponders led only to a significant increase in the numbers of CD4+ T cells and a significant reduction in numbers of activated CD8+/HLA-DR+ T cells. The long-term ability of antiretroviral therapy during early asymptomatic HIV-infection to maintain reversal of disease-induced T-cell activation and maturation abnormalities continues to support the concept that immunologic advantage is gained by commencing early aggressive antiretroviral therapy. Nevertheless, continued management of T-cell subset recovery is significantly more effective in the presence of completely suppressed viral replication.

Anti-HIV Agents↗
PubMed2001

Reduction in cross-sucking in calves by the use of a modified automatic teat feeder.

Cross-sucking may be a problem in group-housed calves fed by automatic teat feeders. In the present study, the behaviour of calves fed by a conventional feeder with an open feeding stall (n=15 calves) was compared with the behaviour of calves fed by a modified feeder, closing in the rear after the calf has entered (n=14 calves). It was found that the calves fed by the feeder with the closed stall stayed longer in the feeding stall following milk ingestion (P<0.001), showed longer bouts of non-nutritive sucking directed to the teat after milk ingestion (P<0.005) and performed less cross-sucking in the first 15min after milk ingestion (P<0.001) than calves fed by the feeder with the open stall. The design of the feeder had, however, no significant influence on the incidence of cross-sucking performed without close temporal association with milk ingestion. As the modification in the feeding stall reduces cross-sucking and is not costly, it should be feasible to introduce it in practice.

Journal Article↗
PubMed2001

Modern anti-HIV therapy.

Highly active antiretroviral therapies (HAART), usually consisting of two nucleoside reverse transcriptase inhibitors (NRTI) plus an HIV protease inhibitor (PI), have been widely used since 1996. They produce durable suppression of viral replication with undetectable plasma levels of HIV-RNA in more than half of patients. Immunity recovers, and morbidity and mortality fall by more than 80% [1, 2]. Treatment was thought to be particularly effective when started early; therefore, HAART was recommended for essentially all HIV-infected persons willing to commit themselves to lifelong therapy [3, 4]. Besides these successes, however, HAART also produces problems. HIV is not eradicated by present-day drugs, and patients often cannot comply with long-term combination treatment [5, 6]. Moreover, HAART causes unexpected and ill-understood side effects [7]. The dogma of earliest possible treatment has therefore come under attack. Ten principles governing anti-retroviral treatment are summarised in Table 1. Starting and maintaining HAART is complex. Within the last few years, the numbers of antiretrovirals, their known and potential interactions with each other and with non-HIV drugs, and the list of their side effects have all increased exponentially. As a rule a physician specialising in HIV care should be consulted whenever HAART is started or changed. It is his task to ensure that the treatment chosen is optimal for the particular patient.

Anti-HIV Agents↗
PubMed2001

Genetic diversity of Pneumocystis carinii in HIV-positive and -negative patients as revealed by PCR-SSCP typing.

OBJECTIVE: To describe the epidemiology of severe Pneumocystis carinii pneumonia (PCP) in HIV-infected and non HIV-infected patients. METHODS: Bronchoalveolar lavage specimens from 212 European patients with PCP were typed using PCR--single strand conformation polymorphism analysis of four genomic regions of P. carinii f. sp. hominis. Demographic and clinical information was obtained from all patients. RESULTS: Twenty-three per cent of the patients were presumably infected with a single P. c. hominis type. The other patients presented with two (50%) or more (27%) types. Thirty-five genetically stable and ubiquitous P. c. hominis types were found. Their frequency ranged from 0.4% to 10% of all isolates, and up to 15% of those from a given hospital. There was no significant association between the P. c. hominis type or number of co-infecting types per patient and geographical location, year of collection, sex, age, or HIV status. No more than three patients infected with the same type were observed in the same hospital within the same 6 month period, and no epidemiological link between the cases was found. CONCLUSIONS: The broad diversity of types observed seems to indicate that multiple sources of the pathogen co-exist. There was no evidence that in our study population inter-human transmission played a significant role in the epidemiology of P. carinii.

Bronchoalveolar Lavage↗
PubMed2001

The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.

OBJECTIVE: To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response. DESIGN: Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml. METHODS: Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count. RESULTS: The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI. CONCLUSIONS: Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation.

Adolescent↗
PubMed2001

Interinstitutional review of thyroid fine-needle aspirations: impact on clinical management of thyroid nodules.

Routine interinstitution pathology consultation can result in change in pathologic diagnosis in up to 10% of patients. In this study, we compared the outside cytopathologic diagnosis of thyroid fine-needle aspiration (FNA) specimens with the in-house diagnosis at the University of Pennsylvania Medical Center over an 18-mo period and its effect on patient management. One hundred ten (60%) diagnostic disagreements were identified among 183 patients. In 16 cases, the diagnosis was changed from benign to malignant, and in 12, the diagnosis was reversed from neoplastic/malignant to benign. Histologic follow-up was available in 109 cases; the overall accuracy of outside diagnosis was 73%, and that of inside diagnosis was 85%. In conclusion, we strongly recommend interinstitution cytology consultation on referred thyroid FNA cases, since our data showed a significant change in diagnosis, thus affecting patient management.

Biopsy, Needle↗
PubMed2001

Phase I clinical trial with HIV-1 gp160 plasmid vaccine in HIV-1-infected asymptomatic subjects.

The aim of the study was to investigate the safety of an HIV-1 gp160 plasmid vaccine. Four asymptomatic HIV-1-infected subjects with CD4+ lymphocyte counts >500/microl were injected with four times 400 microg of HIV-1 modified gp160 env and rev coding DNA vaccine at 0, 4, 10 and 28 weeks. Safety parameters, including autoimmune antibodies as well as CD4+/CD8+ cell counts and HIV-1 plasma concentrations, were monitored for 52 weeks after the first vaccine application. Follow-up data for more than 3 years are now available. The DNA vaccine proved to be safe and, specifically, did not induce anti-DNA autoimmune antibodies. Vaccination had no long-term effects on the CD4+/CD8+ lymphocyte counts, plasma HIV-1 RNA concentrations or disease progression. The present data supplement published data from Philadelphia, USA, where a dose-escalating study (30-300 microg) with the same HIV-1 DNA vaccine was performed.

AIDS Vaccines↗
PubMed2001

Pilot study of interferon-alpha with and without amantadine for the treatment of hepatitis C in HIV coinfected individuals on antiretroviral therapy.

BACKGROUND: Concurrent potent therapy of hepatitis C (HCV) and HIV includes at least five antiviral drugs. Drug interactions, toxicity, tolerance and acceptance by patients of such treatment regimens are unknown. STUDY DESIGN: A prospective open randomized pilot trial was conducted to test interferon-alpha (6 million units/day for the 1st month followed by 6 million thrice weekly) and amantadine versus interferon-alpha monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy. RESULTS: 1,013 HIV-infected patients were consecutively evaluated. 314 were anti-HCV antibody positive; only eight (2.4%) were eligible. Major reasons for exclusion were: normal transaminase levels (34%), ongoing intravenous drug use (33%), or recent change in antiretroviral therapy (31%). Study drugs were stopped in all of the seven patients enrolled because of side effects and/or failure of anti-HCV therapy. CD4 lymphocyte counts and HIV-1 RNA remained stable. CONCLUSION: Among patients on highly active antiretroviral therapy, the addition of interferon-alpha with or without amantadine was inefficient and poorly tolerated, but had no negative influence on HIV infection. Eligibility for the study was unexpectedly low.

Adult↗
PubMed2001

Formation of PCDF, PCDD, PCB, and PCN in de novo synthesis from PAH: mechanistic aspects and correlation to fluidized bed incinerators.

The difference of polychlorinated dibenzofurans (PCDF) isomer patterns between stoker type incinerators and some fluidized bed incinerators (FBI) is a key to understand the formation mechanisms in both types of incinerators. The total yield and the isomer patterns of PCDF, polychlorinated biphenyls (PCB), polychlorinated naphthalenes (PCN), and polychlorinated benzenes (PCBz) formed via de novo synthesis from polycyclic aromatic hydrocarbons (PAH) indicate that chlorinated aromatics in the FBI are formed as a result of PAH breakdown. The detailed analysis of the isomer patterns of PCDF, PCB and PCN gives a first insight into the transformation mechanism of the PAHs and the sequence of degradation, chlorination and oxygen insertion. The major chlorination takes part at the position of the C-C cleavage during degradation of the PAHs. Further chlorination of the hydrogen position of the former PAH takes part preferably in ortho-position to this chlorination or is directed by incorporated oxygen. A perylene structure in soot is proposed as basis for the observed PCDF pattern in the FBI. Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated phenols (PxCP) were formed in lower concentrations from the de novo experiments indicating an additional formation pathway for these compounds in the FBI.

Benzofurans↗
PubMed2001

Formation characteristics of PCDD and PCDF during pyrolysis processes.

In recent years, pyrolysis processes have become technologies developed to industrial scale and discussed as alternatives to the existing waste combustion technology. However, little information is published regarding PCDD/F formation characteristics during pyrolysis processes. Two common shredder fractions--industrial light shredder (ILS) and refrigerators (REF)--both with high chlorine and copper content were pyrolysed for this pyrolysis study using a pilot plant with a capacity of 100 kg/h. At oxygen concentrations below 2% and temperatures between 430 degrees C and 470 degrees C, considerable amounts of PCDD/F were formed during the pyrolysis. More than 90% of total TEQ was found in the oil fraction (gas phase). The PCDD/PCDF ratio and the homologue pattern differed significantly from those formed during waste incineration. Considering mono- to octachlorinated congeners, up to 400 times more PCDF were formed compared to PCDD. For the investigated pyrolysis conditions, the formation of low chlorinated congeners was highly favoured. The distribution of TEQ within the individual congeners were very similar in all investigated runs. More than 80% of total TEQ stem from 2,3,7,8-substituted T4CDF and P5CDF. The isomer pattern, however, did not show significant differences compared to the common waste incineration pattern suggesting that the basic formation routes are similar.

Benzofurans↗
PubMed2001

Effects of chiral fragrances on human autonomic nervous system parameters and self-evaluation.

The effects of chiral fragrances (enantiomers of limonene and carvone) on the human autonomic nervous system (ANS) and on self-evaluation were studied in 20 healthy volunteers. Each fragrance was administered to each subject by inhalation using an A-A-B design. Individuals were tested in four separate sessions; in one session one fragrance was administered. ANS parameters recorded were skin temperature, skin conductance, breathing rate, pulse rate, blood oxygen saturation and systolic as well as diastolic blood pressure. Subjective experience was assessed in terms of mood, calmness and alertness on visual analog scales. In addition, fragrances were rated in terms of pleasantness, intensity and stimulating property. Inhalation of (+)-limonene led to increased systolic blood pressure, subjective alertness and restlessness. Inhalation of (-)-limonene caused an increase in systolic blood pressure but had no effects on psychological parameters. Inhalation of (-)-carvone caused increases in pulse rate, diastolic blood pressure and subjective restlessness. After inhalation of (+)-carvone increased levels of systolic as well as diastolic blood pressure were observed. Correlational analyses revealed that changes in both ANS parameters and self-evaluation were in part related to subjective evaluation of the odor and suggest that both pharmacological and psychological mechanisms are involved in the observed effects. In conclusion, the present study indicates that: (i) prolonged inhalation of fragrances influences ANS parameters as well as mental and emotional conditions; (ii) effects of fragrances are in part based on subjective evaluation of odor; (iii) chirality of odor molecules seems to be a central factor with respect to the biological activity of fragrances.

Adolescent↗
PubMed2001

Modern concepts of frontal sinus surgery.

OBJECTIVES/HYPOTHESIS: To validate the endonasal surgical approach to frontal sinus in inflammatory sinus disease, trauma, and selective tumor surgery, and to define the role of external approaches to the frontal sinus. Endonasal frontal sinusotomy can range from endoscopic removal of obstructing frontal recess cells or uncinate process to the more complex unilateral or bilateral removal of the frontal sinus floor as described in the Draf II-III drainage procedures. In contrast, the osteoplastic frontal sinusotomy remains the "gold standard" for external approaches to frontal sinus disease. METHODS: A retrospective review of 1286 patients undergoing either endonasal or external frontal sinusotomy by the authors at four university teaching programs from 1977. Prior author reports were updated and previously unreported patient series were combined. RESULTS: Six hundred thirty-five patients underwent type I frontal sinusotomy, 312 type II sinusotomy, and 156 type III sinusotomy. A successful result was seen in these groups, 85.2% to 99.3%, 79% to 93.3%, and 91.5% to 95%, respectively. External frontal sinusotomy or osteoplastic frontal sinusotomy was successfully performed in 187 of 194 patients. Clinical symptoms, endoscopic findings, computed tomography, and magnetic resonance image scanning, and reoperation rate measured postoperative success. CONCLUSIONS: A stepwise approach to the surgical treatment of frontal sinusitis, trauma, and selective benign tumors yields successful results as defined by specific criteria which vary from 79% to 97.8%. The details of specific techniques are discussed, essential points emphasized, and author variations noted.

Chronic Disease↗
PubMed2001

Nasopharyngeal endoscopy adds to reliability of clinical diagnosis of infectious mononucleosis.

Frequently, the clinical picture in the oropharynx alone does not lend itself to a reliable differentiation between acute pharyngotonsillitis in infectious mononucleosis and a streptococcal inflammation. Such a differentiation, however, is essential for the indication of antibiotic therapy. Therefore, it was the aim of the present study to investigate whether or not endoscopic verification of larger-than-normal lymphatic tissue with fibrinous membranes in the nasopharynx would enhance the reliability of diagnosis. Fifty hospitalized patients exhibiting the clinical picture of acute pharyngotonsillitis were examined for the following parameters: nasopharyngeal endoscopy, determination of glutamine-oxaloacetic transaminase (GOT), glutamine-pyruvic transaminase (GPT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leucocytes and haemogram, antibodies to viral capsid antigen (VCA)-IgM, Epstein-Barr virus nuclear antigen (EBNA), and cytomegalovirus (CMV). In 24 patients with acute tonsillitis/peritonsillar abscess, and in 26 patients with infectious mononucleosis, the total leucocyte count in the blood and the blood/erythrocyte sedimentation rate were comparable. Atypical lymphocytes or absolute lymphocytosis were not seen in acute tonsillitis, but were found in 88.5 per cent of patients with infectious mononucleosis. Elevated transaminase levels were noted in 77 (GOT) and 88.5 per cent (GPT) of patients with infectious mononucleosis, and in acute tonsillitis in 4.2 (GOT) and 12.5 per cent (GPT) of patients. The CRP was higher than normal in 91.7 per cent of patients with acute tonsillitis, and in 57.7 of patients with infectious mononucleosis. In none of the patients with acute tonsillitis was lymphatic tissue with fibrinous membranes seen in the nasopharyngeal cavity. In contrast, nasopharyngeal endoscopy in infectious mononucleosis was positive in 24 out of 26 patients. Hence, the sensitivity was 92.3 per cent, the specificity 100 per cent, and the prediction value for a positive test turned out to be 1. Endoscopy of the nasopharngeal cavity employed as a simple and supplementary procedure adds to the reliability of diagnosis of infectious mononucleosis.

Adolescent↗
PubMed2001

Penetrance and expressivity of genes involved in the development of epilepsy in the genetically epilepsy-prone rat (GEPR).

In order to understand the level of complexity of the epileptic phenotype in the two strains of Genetically Epilepsy-Prone Rats (GEPRs), we determined two important measures of genetic complexity, penetrance and expressivity. Penetrance is the percentage of animals of a specific genotype who express the phenotype associated with that underlying genotype. Expressivity refers to the degree that a particular genotype is expressed as a phenotype within an individual. Incomplete penetrance and variable expressivity are caused by genetic and environmental variation. In this paper we have studied the epileptic phenotype for 20,373 rats. Animals were tested on three occasions for audiogenic seizure and given an audiogenic response score (on a scale of 0-9, 0 being no seizure and 9 being the most severe). The GEPR-3 and GEPR-9 animals both show incomplete penetrance and variable expressivity of the underlying genetic predisposition. The GEPR-9 strain has more animals that have variable levels of seizure predisposition (as measured by a scoring system that denotes the severity of generalized tonic/clonic seizures) and a greater percentage of animals that exhibit no susceptibility to such seizures induced by sound. Both strains have a number of animals that are not susceptible to sound-induced GTCSs and that exhibit some variability in seizure severity. The GEPR-9 males show greater differences in expressivity and penetrance compared to GEPR-9 females. The GEPR-3 animals also show sex-associated variable penetrance and expressivity of the epileptic phenotype, although the differences are much smaller. These findings are the first step toward the mapping of the underlying quantitative trait loci (QTL) for seizure in these animals.

Animals↗
PubMed2001

Object-oriented business process analysis of the cooperative soft tissue sarcoma trial of the german society for paediatric oncology and haematology (GPOH).

The German Society for Paediatric Oncology and Haematology (GPOH) runs nation-wide multicentre clinical trials to improve the treatment of children suffering from malignant diseases. We want to provide methods and tools to support the centres of these trials in developing trial specific modules for the computer-based DOcumentation System for Paediatric Oncology (DOSPO). For this we carried out an object-oriented business process analysis for the Cooperative Soft Tissue Sarcoma Trial at the Olgahospital Stuttgart for Child and Adolescent Medicine. The result is a comprehensive business process model consisting of UML-diagrams and use case specifications. We recommend the object-oriented business process analysis as a method for the definition of requirements in information processing projects in the field of clinical trials in general. For this our model can serve as basis because it slightly can be adjusted to each type of clinical trial.

Clinical Trials as Topic↗