PubMed Health⌕ Search

Biomedical subjects

A Neumann

Publications and source records attributed to A Neumann.

At least 19 recordsLinked to original sources

Feasibility and low toxicity of early radiotherapy after high-dose chemotherapy and autologous stem cell transplantation for patients with high-risk stage II-III and locally advanced breast carcinoma.

BACKGROUND: This prospective trial examined the feasibility, toxicity, and effectiveness of early locoregional radiotherapy after high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk American Joint Committee on Cancer (AJCC) Stage II-III and locally advanced breast carcinoma. METHODS: One hundred forty-seven consecutive patients with high-risk and locally advanced breast carcinoma were included in the current study. All patients received induction chemotherapy with a doxorubicin-based therapy, which was consolidated with high-dose cyclophosphamide, carboplatin, and thiotepa followed by autologous stem cell support. Within 50 days of the transplant, the patients were treated with locoregional radiotherapy that included the chest wall or breast, the axilla and supraclavicular area, and the internal mammary chain. The volume of lung included in the treatment volume was kept to a minimum. The central lung distance of the tangential fields ranged from 0.6-2.0 cm (mean, 1.1 cm). Tamoxifen was given based on receptor status. RESULTS: One hundred forty-six of 147 patients received the planned treatment. Only six patients had a delay in the initiation of radiotherapy, and another 16 patients had delays during radiotherapy. Leukocyte and platelet toxicities during radiotherapy were not life-threatening and blood counts thereafter returned to normal. Grade 2 (according to National Cancer Institute Common Toxicity Criteria) skin toxicity occurred in 22% of patients and Grade 3 skin toxicity occurred in 6% of patients. Radiation pneumonitis was reported to occur in 5 patients (< 4%). After a median follow-up of 36 months from diagnosis (range, 6-64 months), there were no long-term organ toxicity and no secondary malignancy reported. No treatment-related deaths were reported. Three patients (< 3%) developed locoregional recurrence. CONCLUSIONS: Locoregional radiotherapy after high-dose chemotherapy and autologous stem cell transplantation appears to be feasible and can be delivered safely within 10 weeks of transplantation. The short-term and long-term toxicity are reported to be low, with good local control.

Adult↗

[Use of the Appropriateness Evaluation Protocol in inpatient ENT practice].

BACKGROUND AND OBJECTIVE: Determination of inappropriate hospital use is of increasing importance due to limited resources in health care. The Appropriateness Evaluation Protocol (AEP) serves as an instrument to identify this inappropriate hospital use. It was designed in the USA in 1981 for use in Internal Medicine and General Surgery and consists of criteria items to assess the appropriateness of hospital admissions and days of care. PATIENTS/METHODS: The present study aims to examine the practicability of the AEP in Otorhinolaryngology. The charts of all patients hospitalized in the ENT Department at that particular day were surveyed on 4 consecutive Wednesdays. Three reviewers each reviewed 196 charts. RESULTS: The overall level of inappropriate use was 41.5%. Presuming that the day preoperative to elective surgery was appropriate, the level was 23.1%. CONCLUSIONS: The critical comparison between this result and the actual reasons for hospital admissions and days of care showed, that the present German version of the AEP is less suitable for use in Otorhinolaryngology. Based on the experiences with the AEP an AEP adjusted to Otorhinolaryngology (AEP-ENT) is proposed.

Germany↗

[Clinical aspects of tracheopathia osteoplastica].

Tracheopathia osteoplastica is a rare condition of the tracheobronchial tree characterized by the formation of multiple osseous or cartilaginous submucosal nodules which protrude into the lumen. Clinical features, pathological-anatomical, and radiological findings are described and discussed on the basis of three recent cases and a literature review.Two female patients (age 56 and 62 years) and one male (age 44 years) presented with recurrent tracheobronchitis, a "difficult intubation" at the time of an emergency situation requiring tracheostomy. The diagnosis was confirmed by tracheoscopy. CT scans showed radiodense nodular thickening of the tracheal wall compromising the lumen in all patients, whereas plain chest radiography revealed scalloped linear calcification in only one case. Histologically the nodules consisted of lamellar-type bone covered by normal mucosa. None of the patients needed therapeutic measures as there was no impairment of ventilatory function. The long-term observations (>15 years) of a few authors suggest that the disease is of benign course and does not deteriorate.

Adult↗

[Early surgical pharyngostoma in therapy of postoperative pharyngeal fistulas].

BACKGROUND: Postoperative salivary fistulas after laryngectomy occur in 2-65% of cases according to the literature. They are not only inconvenient but also dangerous, as the permanent leakage of saliva prevents wound healing and may cause a life threatening arrosion hemorrhage from the jugular vein or carotid artery. Spontaneous closure of such fistulas is unlikely unless the leakage of saliva can be reduced sufficiently by suction and wound compression. However, about 50% of these patients develop a mucocutaneous pharyngostome after several weeks or even months, then requiring extensive flap reconstruction. In order to shorten this long rehabilitation process and to protect the patient from the danger of hemorrhage the commonly recommended therapeutic concept was modified in that the saliva was completely drained from the wound by creation of a submental epithelialized pharyngostome. In this paper our 10 year experience with this concept is reported. PATIENTS AND METHOD: During the period from 1991 to 1999 postoperative salivary fistulas were seen in 9 of 94 consecutive patients after total laryngectomy. Right after diagnosis a meticulous surgical wound debridement was performed and a submental pharyngostome was created in each case. After healing of the mucocutaneous lining the pharyngostome itself was closed with regional skin flaps. RESULTS: In 7 of the 9 patients a quick and permanent closure of the fistula was achieved by the treatment described. The sooner after diagnosis of the fistula the pharyngostome was created, the earlier the closure of the fistula was obtained. In 1 patient the pharyngeal reconstruction was complicated by nosocomial infections, 1 patient died in the course of treatment due to non fistula related concomitant disease. CONCLUSIONS: In case of postoperative salivary fistulas following laryngectomy the immediate creation of a mucocutaneous pharyngostome can reduce the duration of treatment and at the same time protect the patient from the danger of vascular arrosion.

Adult↗

Comparison of MPEG-1 digital videotape with digitized sVHS videotape for quantitative echocardiographic measurements.

Digital format is rapidly emerging as a preferred method for displaying and retrieving echocardiographic studies. The qualitative diagnostic accuracy of Moving Pictures Experts Group (MPEG-1) compressed digital echocardiographic studies has been previously reported. The goals of the present study were to compare quantitative measurements derived from MPEG-1 recordings with the super-VHS (sVHS) videotape clinical standard. Six reviewers performed blinded measurements from still-frame images selected from 20 echocardiographic studies that were simultaneously acquired in sVHS and MPEG-1 formats. Measurements were obtainable in 1401 (95%) of 1486 MPEG-1 variables compared with 1356 (91%) of 1486 sVHS variables (P <.001). Excellent agreement existed between MPEG-1 and sVHS 2-dimensional linear measurements (r = 0.97; MPEG-1 = 0.95[sVHS] + 1.1 mm; P <.001; Delta = 9% +/- 10%), 2-dimensional area measurements (r = 0.89), color jet areas (r = 0.87, p <.001), and Doppler velocities (r = 0.92, p <.001). Interobserver variability was similar for both sVHS and MPEG-1 readings. Our results indicate that quantitative off-line measurements from MPEG-1 digitized echocardiographic studies are feasible and comparable to those obtained from sVHS.

Echocardiography↗

Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers.

Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40-50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.

Amino Acid Sequence↗

Adenomatous polyposis coli I1307K mutation in Jewish patients with different ethnicity: prevalence and phenotype.

BACKGROUND: A new mutation, I1307K, recently was reported in the adenomatous polyposis coli (APC) gene. This mutation was found to be predominant in Ashkenazi Jews, creating a hypermutable area and predisposing the development of carcinoma. The objective of the current study was to estimate the prevalence of this mutation in several of the ethnic groups that comprise the Israeli population and to elucidate the clinical features of the mutation carriers with colorectal carcinoma (CRC). METHODS: A total of 111 consecutive CRC patients were evaluated and their medical history and clinical data recorded. The general population (298 Ashkenazim and 189 Yemenites) also was tested for the presence of this mutation. Mutation screening was performed using both the polymerase chain reaction-based amplification refractory mutation system and a commercial APC kit. RESULTS: Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mutation and 26 of 487 subjects from the general population (5.3%) carried the I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there were 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general population (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yemenite origin, 3 carried the mutation and 9 carriers were found among 189 subjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late age at diagnosis (64.6 years +/- 10.0, which is similar to that of the noncarriers), mostly right-sided tumors, and moderate to good differentiation constituted the phenotype of the mutation carriers. CONCLUSIONS: The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is prevalent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance.

Adenomatous Polyposis Coli↗

[Management of complications after prosthetic voice rehabilitation].

The growing popularity of prosthetic voice restoration after total laryngectomy confronts ENT specialists with an increasing number of prosthesis-related complications. The ENT specialist should be familiar with the management of these complications in order to maintain the patients speech and social rehabilitation. In a retrospective study on 108 consecutive patients, complications were encountered in 30%. The incidence was not related to the factors age or primary vs. secondary insertion of the prosthesis. Complications consisted of formation of granulation tissue (15.7%), shunt dilatation (5.5%), loss of prosthesis (3.7%), local cellulitis (2.8%), extrusion (1.9%), ingrowth of prosthesis (1.9%) and formation of excessive scar tissue with dislocation of prosthesis (0.9%). Permanent removal of the prosthesis due to complications was necessary in 3 cases (2.8%). Therapeutic measures for the management of complications are described and evaluated. The treatment of complications was well tolerated by all patients and led to satisfying results in most cases. Our observations show that prosthetic voice rehabilitation is associated with various difficulties and complications, but that these can be handled quite easily and successfully in the majority of cases.

Adult↗

A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia.

BACKGROUND: Endotoxin (lipopolysaccharide [LPS]) has been associated with sepsis and the high mortality rate seen in septic shock. The administration of a small amount of LPS to healthy subjects produces a mild syndrome qualitatively similar to that seen in clinical sepsis. We used this model to test the efficacy of an endotoxin antagonist, E5531, in blocking this LPS-induced syndrome. METHODS: In a placebo-controlled, double-blind study, we randomly assigned 32 healthy volunteers to four sequential groups (100, 250, 500, or 1000 microg of E5531). Each group of eight subjects (six assigned to E5531, two assigned to placebo) received a 30-min intravenous infusion of study drug. LPS (4 ng/kg) was administered to all subjects as an intravenous bolus in the contralateral arm at the midpoint of the infusion. Symptoms, signs, laboratory values, and hemodynamics (by echocardiogram) were evaluated at prospectively defined times. RESULTS: In subjects receiving placebo, LPS caused headache, nausea, chills, and myalgias. E5531 led to a dose-dependent decrease in these symptoms that was statistically significant (p < .05) except for myalgias. The signs of endotoxemia (fever, tachycardia, and hypotension) were consistently inhibited at the three higher doses (250, 500, and 1000 microg, p < .05). Tumor necrosis factor-alpha and interleukin-6 blood levels were both lower in those who received E5531 (p < .0001). The C-reactive protein level and white blood cell count response were decreased at all doses (p < .0001). The hyperdynamic cardiovascular state (high cardiac index and low systemic vascular resistance) associated with endotoxin challenge was significantly inhibited at the higher doses of E5531. CONCLUSIONS: E5531 blocks the symptoms and signs and cytokine, white blood cell count, C-reactive protein, and cardiovascular response seen in experimental endotoxemia. This agent is a potent inhibitor of endotoxin challenge in humans and may be of benefit in the prevention or treatment of sepsis and septic shock.

Adolescent↗

High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappaB activation and cytokine expression.

Advanced glycation endproducts (AGEs), which accumulate on long-lived proteins and protein deposits (amyloids), induce the expression of proinflammatory cytokines through NF-kappaB-dependent pathways. Hyaluronic acid with a molecular weight above 1.2 MDa (HMW-HA) inhibits the AGE-induced activation of the transcription factor NF-kappaB and the NF-kappaB-regulated cytokines interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha. Since the molecular weight of hyaluronic acid in humans decreases with age and under conditions of oxidative stress, it is likely that the protective effect of HMW-HA against AGE-induced cellular activation is lost at sites of chronic inflammation and in older age.

Animals↗

T cell repertoire alterations of vascularized xenografts.

The role of T cells in the rejection of vascularized xenografts has been little explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterations in molecular interactions could impair the T cell response. Because the analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipients treated with a combination of cobra venom factor and cyclosporin A (CsA), to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rejected xenografts, compared with allografts. After withdrawal of CsA (on day 40), the analysis of V beta family expression and corresponding complementarity-determining region 3 lengths in rejected xenografts revealed a Gaussian pattern, in contrast to a much more restricted pattern in rejected allografts (p = 0.002), suggesting that, after withdrawal of CsA, all the underrepresented T cell clones are rapidly expanded in xenografts. These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high number of T cells, the rapid expression of markers of activation (IL-2 receptor alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts. Taken together, these results suggest that the intensity and diversity of the T cell response to xenografts could be stronger than the response to allografts in vivo.

Animals↗

Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers.

We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic. Functional analysis confirms that these mutations inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII. The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.

Adult↗

Is bradykinin a mediator of renal neuropeptide Y effects?

We have previously reported that the bradykinin receptor antagonist icatibant attenuates the neuropeptide-Y-induced diuresis and natriuresis in anaesthetized rats (Am J Physiol 275:F502-F509, 1998). Therefore, we have now determined whether bradykinin mimics tubular responses to neuropeptide Y in acutely pentobarbital-anaesthetized rats. Infusion of the neuropeptide Y receptor agonist peptide YY (2 micrograms kg-1 min-1) enhanced diuresis and natriuresis approximately equal to 2- and 4-fold, respectively, but did not increase urinary bradykinin excretion. Intrarenal infusion of bradykinin (100 ng kg-1 min-1) reduced renal blood flow by approximately equal to 12% and this was abolished by concomitant administration of icatibant (200 ng kg-1 min-1). However, intrarenal bradykinin infusion did not affect creatinine clearance, urine flow rate or sodium excretion (basal values: 0.8 ml min-1, 111 microliters/15 min and 7.7 mumol/15 min, respectively). These data do not support our original hypothesis that bradykinin mediates the renal effects of neuropeptide Y.

Animals↗

Maternal UPD 20 in a hyperactive child with severe growth retardation.

Maternal uniparental disomy was observed in a 4-year-old boy with severe pre- and postnatal growth retardation (body height: 85 cm = 12 cm < third percentile, head circumference: 48 cm = 10 cm < third percentile), a few minor facial findings, and with apparent hyperactivity. His intelligence is within the normal range for his age. Karyotype analysis revealed two cell lines, one apparently normal with 46,XY, the other with a tiny marker (47,XY, + mar). Microdissection and reverse chromosome painting using the marker DNA library as a probe, as well as PCR analysis revealed that the marker is from chromosome 20 and contains only the centromere and pericentromeric segments, but none of the pericentromeric loci for microsatellites. Microsatellite analysis of 25 chromosome 20 loci disclosed maternal uniparental disomy for all 16 informative markers. Maternal heterodisomy was evident for seven loci of the short arm segment 20p11.2-pter. Maternal isodisomy was found at five loci, three of them map to the proximal 20p11.2 segment and two to 20q. To our knowledge, this is the first case of maternal disomy 20 in humans.

Child Behavior Disorders↗

[Effect of lactation state (1st-20th week of lactation) on dynamics of C-reactive protein (CRP) in initial quarter milk samples in relation to somatic cell count, lactose content and blood serum CRP levels].

The concentration of C-reactive protein (CRP) in milk and blood serum varies during the first half of lactation. Somatic cell count and lactose content also depend on the stage of lactation. CRP blood serum levels show a distinct tendency to increase from the 2nd to the 20th week of lactation. In contrary the milk CRP content decreases from the 1st week to the end of the 2nd month post partum and increases again from the 8th to the 20th week post partum. Somatic cells and CRP-concentrations in milk increase parallelly but the lactose content shows a contrary pattern in the first five months of lactation.

Animals↗

[Investigations on the behavior of C-reactive protein, cell count, lactose content as well as electric conductivity in quarter milk samples of subclinically diseased quarters of the udders in relation to bacteriologic results].

Inflammations of the udder influence the amount of somatic cells and lactose as well as electrical conductivity in milk. They are often caused by bacterial agents. Similar reactions are to be seen in relation to C-reactive protein (CRP). The amount of CRP in milk depends on concentration and characteristics of the agents and the phase of inflammation. We found a significant increase of CRP in milk samples with Streptococcus (Sc.) uberis. There was no significant difference in CRP concentrations in samples with coagulase positive Staphylococcus spp. (CPS) and bacteriological negative samples and such with Corynebacterium (C.) bovis, Micrococcus spp. and Staphylococcus (S.) epidermidis. We only found high correlations to the amount of somatic sells and lactose as well as electrical conductivity in samples with Sc. uberis. The results of our investigations show that CRP may be a parameter for better understanding subclinical inflammations of udder.

Animals↗