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Biomedical subjects

M Busch

Publications and source records attributed to M Busch.

At least 37 records · Page 2Linked to original sources

Differences in the temporal trends of HIV seroincidence and seroprevalence among sexually transmitted disease clinic patients, 1989-1998: application of the serologic testing algorithm for recent HIV seroconversion.

The authors compared temporal trends in the prevalence and incidence of human immunodeficiency virus (HIV) infection based upon 34,866 specimens from patients who attended the San Francisco, California, municipal sexually transmitted disease clinic between 1989 and 1998. HIV infection data were collected during annual blinded HIV serologic surveys. Incidence was determined by applying a serologic testing algorithm for recent HIV seroconversion that uses both a sensitive and a less sensitive enzyme immunoassay to stored HIV positive sera. The HIV seroprevalence declined from 15.2% in 1989 to 7.2% in 1998 (odds ratio per year = 0.92, 95% confidence interval (CI): 0.91, 0.94). Among homosexual men, the HIV prevalence declined from 50.9% in 1989 to 19.9% in 1998 (odds ratio per year = 0.86, 95% CI: 0.85, 0.88). The pooled seroincidence was 1.6% and did not change significantly over time (odds ratio per year = 1.0, 95% CI: 0.98, 1.1). The pooled seroincidence among homosexual men was 6.6% per year and remained steady between 1989 and 1998 (odds ratio per year = 0.99, 95% CI: 0.92, 1.1). During a dramatic, 10-year decline in seroprevalence of HIV infection, the incidence of HIV infection remained remarkably stable.

Adult↗

Nucleosomes in serum of patients with benign and malignant diseases.

High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.

Cell Death↗

Reduction in CD8+ cell noncytotoxic anti-HIV activity in individuals receiving highly active antiretroviral therapy during primary infection.

Recent advances in the ability to detect people at the early stages of HIV infection now permit the initiation of antiretroviral treatment before the full complement of antiviral immune responses has evolved. However, the influence of early treatment interventions on the developing anti-HIV immune response is unknown. This study investigates the impact of standard highly active antiretroviral therapy (HAART) during the primary stages of HIV infection on the plasma HIV-1 RNA level, CD4(+) and CD8(+) lymphocyte counts, and the CD8(+) cell anti-HIV response. Individuals treated with HAART within 6 months of infection showed dramatic and rapid reductions in HIV-1 RNA levels along with modest increases in CD4(+) cell number and decreases in CD8(+) cell numbers. A significant reduction in the level of CD8(+) cell noncytotoxic suppression of HIV replication was observed over time in most participants receiving HAART. Importantly, those individuals choosing not to receive therapy maintained low but detectable HIV-1 RNA levels and showed no reduction in their CD8(+) cell antiviral response. These results suggest that either continued antigenic challenge is required to sustain CD8(+) cell-mediated anti-HIV activity, or that HAART has some inhibitory effect on this important immunologic function during the early stages of infection.

Adult↗

Homocysteine, its metabolites, and B-group vitamins in renal transplant patients.

BACKGROUND: Increased plasma total homocysteine (tHcy) levels are an independent risk factor for cardiovascular morbidity in patients with normal and impaired renal function, including stable renal transplant recipients (RTRs). Plasma concentrations of the metabolites of Hcy, such as cystathionine (Cys), methylmalonic acid (MMA), 2-methylcitric acid (MC), and its diastereomers MCI and MCII have been reported in only a few articles. We therefore looked for the serum concentration of these metabolites and their relationship to renal function, cardiovascular diseases, the immunosuppressive treatment, and serum concentrations of cobalamin and folate. METHODS: Fifty RTRs (mean age 50.4 +/- 11.8 years, 35.9 +/- 44.4 months after kidney transplantation) and 35 controls (NP; mean age 43.5 +/- 14.4 years) were studied. Total Hcy and its metabolites were measured by gas chromatography-mass spectrometry (GC-MS). RESULTS: Total Hcy, MMA, Cys, and MC were elevated twofold to sixfold as compared with NP, with a significant interrelationship between these compounds. With the exception of Cys, they were significantly correlated with serum creatinine. Serum folate levels were inversely correlated with tHcy, Cys and cobalamin with MMA and the ratio of MCI/MCII. There was no correlation between tHcy concentration and its metabolites with immunosuppressive treatment (CsA vs. FK506), clinical history, or current findings of cardiovascular complications and blood pressure profile. CONCLUSION: Prospective studies are needed to find out whether the lowering or normalization of serum concentrations of tHcy and its metabolites due to treatment with B vitamins should be achieved to reduce the cardiovascular risk and improve the long-term outcome of allografts and of patients.

Adult↗

Environmental factors associated with rodent infestations in Argentine poultry farms.

1. Seasonal variations in rodent infestations were studied at poultry farms in central Argentina as well as the environmental factors associated with rodent infestations at poultry farms. 2. During the summer and winter of 1998 rodent infestation was monitored at 10 poultry farms by means of tracking stations, and 21 environmental variables were selected that a priori could be related with the extent of rodent infestation. 3. There was a higher rodent infestation in winter than in summer. 4. Species detected by rodent sightings at the poultry farms included Akodon azarae, Calomys spp. (C. laucha and possibly C. musculinus) and Mus musculus. 5. In summer, rodent infestation was positively associated with the perimeter of the farm, whereas there was an inverse relationship with the maintenance conditions of the sheds. In winter, rodent infestation was positively associated with the percentage of the borders of the farm covered with vegetation, and with the amount of plant cover, especially the amount of plant cover which was above 20 cm in height. 6. There was no significant relationship between rodent infestation and the time lag since the last application of rodenticide (first-generation anticoagulant) at the farms. 7. These results suggest that strategies for controlling rodents based solely on chemical methods may not be good enough for efficient rodent control. Farms which are properly managed, with a better control of vegetation growth at both the perimeter and within the internal area, in addition to a higher maintenance of sheds have appreciably lower rodent infestations.

Animal Husbandry↗

The active magnetic resonance imaging stent (AMRIS): initial experimental in vivo results with locally amplified MR angiography and flow measurements.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) is limited by artifacts in vessels after stenting. An active MR imaging stent (AMRIS) allows for artifact-free imaging with local improvement in signal-to-noise ratio (SNR). In a rabbit model, we evaluated the imaging properties by MR angiography (MRA) and flow measurements. METHODS: The AMRIS was placed in the abdominal aorta of five rabbits. At 1.5 T, MRA (three-dimensional fast low-angle shot) was performed before and after intravenous injection of an iron oxide-based, blood-pool contrast medium (dose, 50 micromol Fe/kg), and flow measurements were performed (electrocardiographically triggered phase-contrast cine gradient-echo sequence). Mean SNRs were calculated and flow volume curves were generated. RESULTS: The SNR was 6.0 +/- 0.6 (outside the stent) versus 12.3 +/- 1.1 (inside the stent, P < 0.05) for plain MRA, 21.2 +/- 0.6 versus 40.6 +/- 5.2 (P < 0.05) for contrast-enhanced MRA, and 5.4 +/- 0.4 versus 13.7 +/- 2.1 (P < 0.05) for the magnitude images of flow measurements. Flow volume curves within and distal to the stent were comparable. CONCLUSIONS: By using the AMRIS as a vascular stent, the stented vessel segment can be examined with enhanced signal intensity on MRI.

Animals↗

Circulating nucleosomes in serum.

In the nucleus of eukaryotic cells, DNA is associated with several protein components and forms complexes known as nucleosomes. During cell death, particularly during apoptosis, endonucleases are activated that cleave the chromatin into multiple oligo- and mononucleosomes. Subsequently, these nucleosomes are packed into apoptotic bodies and are engulfed by macrophages or neighboring cells. In cases of high rates of cellular turnover and cell death, they also are released into the circulation and can be detected in serum or plasma. As enhanced cell death occurs under various pathologic conditions, elevated amounts of circulating nucleosomes are not specific for any benign or malignant disorder. However, the course of change in the nucleosomal levels in circulation of patients with malignant tumors during chemotherapy or radiotherapy is associated with the clinical outcome and can be useful for the therapeutic monitoring and the prediction of the therapeutic efficacy.

Antineoplastic Agents↗

Receptor-ligand interactions studied with homogeneous fluorescence-based assays suitable for miniaturized screening.

Cell membrane receptors play a central role in controlling cellular functions, making them the target of drugs for a wide variety of diseases. This report describes how a recently developed method, fluorescence intensity distribution analysis (FIDA), can be used to develop homogeneous, nonradioactive high throughput screening assays for membrane receptors. With FIDA, free ligand and ligand accumulated on receptor-bearing membrane vesicles can be distinguished on the basis of their particle brightness. This allows the concentration of both bound and free ligand to be determined reliably from a single measurement, without any separation. We demonstrate that ligand affinity, receptor expression level, and potency of inhibitors can be determined using the epidermal growth factor and beta(2)-adrenergic receptors as model systems. Highly focused confocal optics enable single-molecule sensitivity, and sample volumes can thus be reduced to 1 microl without affecting the quality of the fluorescence signal. Our results demonstrate that FIDA is an ideal method for membrane receptor assays offering substantial benefits for assay development and high throughput pharmaceutical screening.

Betacellulin↗

Ligand binding to transmembrane receptors on intact cells or membrane vesicles measured in a homogeneous 1-microliter assay format.

We have developed homogeneous miniaturized assays to measure ligand binding to either intact cells or receptor-containing membrane fragments by analysis of particle brightness. As an example, the affinities and inhibition constants of fluorescently labeled interleukin-8 (IL-8) and a low-molecular-weight antagonist toward the receptors CXCR1 and CXCR2, which belong to the superfamily of G protein-coupled receptors (GPCRs), were determined. Although the results were generally comparable between the two approaches, the cell-based measurements revealed a more complex pattern of both ligand and inhibitor titration curves, pointing to the influence of intracellular regulatory events. Both the vesicle- and cell-based membrane receptor assays were successfully miniaturized to a total volume of 1 microl without compromising their sensitivity, indicating that screening of transmembrane receptors in these formats is feasible. This is the first report of a cellular ligand-binding assay performed in such low volumes. The resulting savings in reagent could potentially enable the use of primary cells for future HTS/ultra-HTS efforts.

Animals↗

Excitation functions of the analyzing power in pp--> scattering from 0.45 to 2.5 GeV

Excitation functions A(N)(p(p),Theta(c.m.)) of the analyzing power in pp--> elastic scattering have been measured with a polarized atomic hydrogen target for projectile momenta p(p) between 1000 and 3300 MeV/ c. The experiment was performed for scattering angles 30 degrees </=Theta(c.m.)</=90 degrees using the recirculating beam of the proton storage ring COSY during acceleration. The resulting excitation functions and angular distributions of high internal consistency have significant impact on the recent phase shift solution SAID SP99, in particular, on the spin triplet phase shifts between 1000 and 1800 MeV, and demonstrate the limited predictive power of single-energy phase shift solutions at these energies.

Journal Article↗

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II.

PURPOSE: Between 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors. METHODS AND MATERIALS: Ninety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates. RESULTS: Five-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and-with only marginal significance-radiation doses to the vulva. CONCLUSIONS: The prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the vulva should be irradiated resulting in better long-term survival.

Adult↗

Effect of long-term dietary protein intake on glucose metabolism in humans.

AIMS/HYPOTHESIS: A meal rich in protein stimulates insulin secretion. Long-term effects of dietary protein on insulin release and glucose metabolism are, however, still not known. Our study focussed on the effect of different protein intake on pancreatic insulin secretion capacity, glycogen turnover and gluconeogenesis. METHODS: Subjects with constant (6 months) dietary protein of 1.87 +/- 0.26 g kg(-1) day(-1) (1.25-2.41) named high protein group and with 0.74 +/- 0.08 (0.57-0.80), normal protein group, were identified by a food questionnaire and were matched (n = 9) according to sex, age and calorie intake. They underwent an intravenous glucose tolerance test and a euglycaemic hyperinsulinaemic clamp with infusion of [6,6-2H2]-glucose combined with indirect calorimetry. To estimate net gluconeogenesis the usual diet was enriched by deuterated water or U-[13C6]-glucose and breath and plasma were sampled. RESULTS: Glucose-stimulated insulin secretion was increased in the high protein group (516 +/- 45 pmol/l vs 305 +/- 32, p = 0.012) due to reduced glucose threshold of the endocrine beta cells (4.2 +/- 0.5 mmol/l vs 4.9 +/- 0.3, p = 0.031). Endogeneous glucose output was increased by 12% (p = 0.009) at 40 pmol/l plasma insulin in the high protein group, but not at higher insulin concentration whereas overall glucose disposal was reduced. Fasting plasma glucagon was 34% increased in the high protein group (p = 0.038). Fractional gluconeogenesis was increased by 40% in subjects receiving a high protein diet as determined by both methods. CONCLUSION/INTERPRETATION: High protein diet is accompanied by increased stimulation of glucagon and insulin within the endocrine pancreas, high glycogen turnover and stimulation of gluconeogenesis.

Adult↗

Influence of column geometry on the ion chromatographic separation of aluminium species.

The dependence of the degree of disintegration and therefore the applicability of ion chromatography for the speciation of aluminium fluoride species was examined for two different column geometries, a standard bore and a microbore column. Besides mathematical calculations, the temperature of the separation column was varied between -5 and 50 degrees C for the observation of a temperature-dependent decomposition of the species. All species were detected by UV photometry after post-column reaction with Tiron. The results showed that the disintegration of the higher coordinated Al fluoride species (AlFn with n >2) could be dramatically reduced utilizing the microbore technique. In contrast to the standard bore technique the column temperature is of minor importance. The agreement between speciation data experimentally determined by microbore chromatography and those calculated using stability constants is quite good. The standard bore technique showed bigger differences between calculated and experimentally determined species distributions.

Journal Article↗

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser -- preliminary results.

BACKGROUND AND OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS AND METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Adult↗

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI).

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Female↗

Occurrence of chlamydiae in the genital tracts of sows at slaughter and their possible significance for reproductive failure.

The aim of this study was to investigate further the role of chlamydiae as pathogens in the genital tracts of sows at slaughter. Genital tracts of 101 randomly selected sows were collected and specimens of genital tract localizations were systematically examined for chlamydiae using immunohistochemistry and PCR. In the genital tracts of 10 sows, Chlamydia psittaci DNA was detected by PCR, and was further typed as 'serotype 1' in nine cases and as avian strain 6 BC in one animal. However, all specimens examined by immunohistochemistry were negative for chlamydiae. Pooled samples of scalding tank water were additionally investigated for 95 animals. Of these samples, 63.2% contained chlamydial DNA, mostly C. trachomatis, and in one sample C. psittaci 'serotype 1'. Although in most cases contamination through influx of faecally contaminated scalding water is a possible reason for the positive PCR results in the genital tract, latent infection cannot be excluded. In conclusion, the results obtained suggest that chlamydiae are of no or only minor importance in the examined group of Swiss breeding sows. Nevertheless, the role and significance of chlamydiae as pathogens in porcine reproductive disorders remain unresolved and require further investigation.

Animals↗

Immune response to blood transfusion invery-low-birthweight infants.

BACKGROUND: Allogeneic blood transfusion is common in the treatment of neonatal anemia of prematurity or anemia due to multiple phlebotomies. The immune response of neonates to passenger leukocytes from allogeneic red cells was investigated. STUDY DESIGN AND METHODS: Fourteen infants (4 male, 10 female) prospectively were randomly assigned to receive either white cell-reduced (Group 1) or non-white-cell reduced (Group 2) irradiated blood. Blood samples were taken before and at various time intervals after transfusion (Days 1, 5-7,and 10-14). Cord blood from 11 healthy term infants was used for comparison. The following surface markers were used to assess immune modulation by flow cytometry: CD45RA/CD45RO, CD4/CD8, CD25/CD28, CD3/DR, CD14/B7, and CD3/CD56+CD16. Donor cell microchimerism was studied using semi-quantitative polymerase chain reaction Y-chromosome detection in female infants who received male donor blood. Donor and recipient HLA class II typing was performed with polymerase chain reaction with sequence specific primers. RESULTS: The lymphocyte counts in both groups were significantly increased after transfusion, and there was a significant increase in lymphocytes expressing CD45RA, CD3-/CD16+CD56, CD80, and CD3-/DR on Day 14. The premature infants' pretransfusion natural killer cell population (CD3-/CD16+CD56) was significantly lower than that of term infants, but it reached a similar level by Days 10-14. CD8 subpopulations were increased but not CD4+ cells. Two female infants (of 6) had circulating Y chromosomes 1 day after transfusion, and most of the infants effectively cleared the donor cells within 24 hours of transfusion. Two Group 2 infants who by chance received presumably HLA-haploidentical donor blood developed necrotizing enterocolitis. CONCLUSION: Blood transfusion alters immune cell antigen expression in premature neonates and may initially be immunostimulatory and later immunosuppressive.

Anemia, Neonatal↗

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗