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Biomedical subjects

Thomas Meyer

Publications and source records attributed to Thomas Meyer.

At least 19 recordsLinked to original sources
PubMed2006

Contrast enhanced sonography of the gallbladder: a tool in the diagnosis of cholecystitis?

RATIONALE AND OBJECTIVES: To evaluate if contrast enhanced sonography (CES) can help to detect gallbladder inflammation and differentiate between acute and chronic cholecystitis. MATERIALS AND METHODS: Thirty-three patients with clinical suspicion of acute cholecystitis were examined with CES before cholecystectomy. Thirty patients with no history of gallbladder disease served as control. CES was performed using 2.5 mL SonoVue. A small mechanical index was chosen (0.1). The enhancement pattern of the gallbladder was ranked in a three-point scale: no enhancement, low enhancement and strong enhancement. 28/33 patients underwent surgery. Sonographic findings were compared to histological results. RESULTS: In 16/20 cases with histological proven acute cholecystitis, the gallbladder wall showed a strong enhancement. Low enhancement was found in four patients with acute and in six patients with chronic cholecystitis. The gallbladder wall of two patients with chronic inflammation and all patients (30/30) of the control group showed no enhancement. CONCLUSION: CES is a feasible tool for detecting gallbladder inflammation. Differentiating between acute and chronic cholecystitis seems to be possible.

Acute Disease↗
PubMed2006

Surgical management of pulmonary metastases from colorectal cancer in 153 patients.

BACKGROUND: Surgery has become a recognized therapeutic means in selected patients with pulmonary metastases from colorectal origin. We reviewed our experience in the surgical treatment of 153 patients with pulmonary colorectal metastases and investigated factors affecting survival. METHODS: A retrospective analysis of the records of all patients (n = 153) with pulmonary metastases from colorectal cancer who underwent thoracotomy between 1978 and 2003 at a single surgical center was performed. RESULTS: One hundred fifty-three patients with pulmonary metastases from colon (n = 61) or rectal (n = 92) cancer underwent 180 thoracotomies. The 2- and 5-year probabilities of survival after the first thoracotomy were 64% and 37%, respectively. Sex, age, site, International Union Against Cancer stage of the primary tumor, prethoracotomy carcinoembryonic antigen level, size of metastases, and previous resection of hepatic metastases were not found to be statistically significant prognostic factors. Number of metastases (solitary vs. multiple), mode of operation (wedge vs. anatomical resection), disease-free interval (DFI; > 36 months), negative hilar or mediastinal lymph node status, resection margin > 10 mm, and administration of intraoperative blood substitution were predictors of a longer survival duration by univariate analysis, but only number of metastases (P = .019), mode of operation (P = .004), DFI (P = .027), and intraoperative blood substitution (P = .002) were identified as independent prognostic factors by multivariate analysis. CONCLUSIONS: Pulmonary resection for metastases from colorectal cancer is safe and results in long-term survival in selected patients. Single metastases, anatomical resection, intraoperative blood substitution, and DFI > 36 months seem to be the most reliable predictors of survival.

Adult↗
PubMed2006

Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling.

BACKGROUND: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC). RESULTS: Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p < 0.05). Verification of 13 up- or down-regulated genes was performed by quantitative real-time reverse transcription (RT)-PCR and genes were additionally confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. CONCLUSION: The majority of identified differentially expressed genes in cutaneous SCC were previously not described.

Adolescent↗
PubMed2006

Aromatic interactions with phenylalanine 691 and cysteine 828: a concept for FMS-like tyrosine kinase-3 inhibition. Application to the discovery of a new class of potential antileukemia agents.

FLT3 kinase inhibitors are currently under investigation as a new treatment for acute myeloid leukemia. We report here a molecular concept invoking interactions between an aromatic ring and the side chains of Phe691 and Cys828, two residues of the ATP pocket, to obtain potent and specific inhibitors of this kinase. The hypothesis has been validated by the successful design of a new inhibitor prototype showing promising antiproliferative activity in cellular assays.

Acute Disease↗
PubMed2006

AM-111 protects against permanent hearing loss from impulse noise trauma.

The otoprotective peptide AM-111, a cell-permeable inhibitor of JNK mediated apoptosis, was tested for its efficacy as a rescue agent following impulse noise trauma. Single dose administrations of AM-111 at 1h or 4h post-impulse noise exposure (155 dB peak SPL) via systemic or local routes were evaluated with a total of 48 chinchillas. The animals received the compound either by IP injection or locally onto the round window membrane (hyaluronic acid gel formulation or osmotic mini-pump). Efficacy was determined by auditory brainstem responses (ABR) as well as cytocochleograms. Three weeks after impulse noise exposure, permanent threshold shifts (PTS) were significantly lower for AM-111 treated ears compared to controls, regardless of the drug administration route and the time point of drug delivery. Even the treatments which started 4h post-noise exposure, reduced hearing loss in the 2-8 kHz range compared to controls by up to 16-25 dB to a PTS as low as 6-17 dB, demonstrating significant protection against permanent hearing loss from impulse noise trauma. These findings suggest a key role for JNK mediated cochlear sensory cell death from oxidative stress.

Animals↗
PubMed2006

Breakpoint cloning and haplotype analysis indicate a single origin of the common Inv(10)(p11.2q21.2) mutation among northern Europeans.

The pericentric inv(10)(p11.2q21.2) mutation has been frequently identified in cytogenetic laboratories, is phenotypically silent, and is considered to be a polymorphic variant. Cloning and sequencing of the junction fragments on 10p11 and 10q21 revealed that neither inversion breakpoint directly involved any genes or repetitive sequences, although both breakpoint regions contain a number of repeats. All 20 apparently unrelated inv(10) families in our study had identical breakpoints, and detailed haplotype analysis showed that the inversions were identical by descent. Thus, although considered a common variant, inv(10)(p11.2q21.2) has a single ancestral founder among northern Europeans.

Base Sequence↗
PubMed2006

A new biocompatible material (Lyoplant) for the therapy of congenital abdominal wall defects: first experimental results in rats.

Congenital abdominal wall defects are impressive and dramatic malformations. Common surgical therapy for omphalocele and gastroschisis is to place the herniated viscera back into the abdomen and to close the fascia. Small defects can be closed directly by surgical treatment. In large defects, resorbable and non-resorbable artificial materials are necessary to close the fascia. The aim of this study is to find out whether new biocompatible materials might be suitable for the treatment of such abdominal wall defects. A median laparotomy was performed in young Wistar rats with a body weight of 75-100 g. Then a full thickness defect was created by excising a 1.5 x 2.5 cm segment including fascia, muscles and peritoneum. These defects were then closed by implantation of a PTFE mesh (Dual-Mesh, n = 6), a PPP mesh (Prolene, n = 6) or a new biocompatible mesh (NBM; Lyoplant, n = 6). Each rat was examined daily after treatment. Bodyweight was determined and the possible development of a hernia was monitored. After 6 weeks, the abdomen was opened again. Adhesions to the intestine were measured and the abdominal wall was removed for histological and tensiometric examination. (1) Compared to the untreated controls, all animals showed physiologic growth and normal bodyweight curve. (2) Only in one rat (Prolene) did an abdominal hernia develop. (3) In contrast to PTFE and PPP mesh, NBM showed only minimal adhesion to the intestine. (4) Tensiometry revealed high stability for non-resorbable materials. However, the characteristics of NBM were very similar to untreated abdominal wall. Our initial results indicate that biocompatible materials can also be used for the therapy of congenital abdominal wall defects.

Abdominal Wall↗
PubMed2006

Maintenance chemotherapy after chemoradiation improves survival of patients with locally advanced pancreatic carcinoma: a retrospective analysis of prospectively recruited patients.

BACKGROUND AND PURPOSE: Currently, there is no treatment standard for patients with locally advanced pancreatic cancer (PaCa) after chemoradiation. The aim of the present study was to retrospectively assess overall survival and toxicity of chemotherapy in addition to chemoradiation in this patient group. PATIENTS AND METHODS: Three-dimensional conformal irradiation to the primary tumor (55.8 Gy) and the lymphatics (50.4 Gy) was combined with 5-fluorouracil- or gemcitabine-based chemotherapy followed by additional chemotherapy with gemcitabine until progression or no further treatment. Decision for chemotherapy was taken at the discretion of the attending physician considering the patient's desire. RESULTS: A total of 172 patients were addressed to the local tumor board. Patients with (neo)adjuvant treatment or metastatic disease were excluded (n = 90). 82 patients were treated with chemoradiation and had additional chemotherapy (n = 40) or no further treatment (n = 42). Characteristics of the two groups were equally distributed. Patients with chemotherapy had significantly longer overall survival as compared to patients without (13 months vs. 8 months; p < 0.0001; median survival = 10.7 months for all patients). Acute toxicity of maintenance chemotherapy was relatively mild. CONCLUSION: Maintenance chemotherapy after chemoradiation for patients with locally advanced PaCa may significantly increase survival rates without severe side effects and is therefore recommended as standard treatment following chemoradiation.

Adult↗
PubMed2006

In vitro comparison of two delivery devices for administering formoterol: Foradil P and formoterol ratiopharm single-dose capsule inhaler.

Formoterol, a long-acting beta (2)-agonist with a rapid onset of bronchodilation, is available in various delivery devices. However, differences in the size and uniformity of drug particles generated by different devices may result in variable clinical effects. The present study compared in vitro the aerodynamic particle size distribution, emitted dose and device resistance of formoterol delivered via Foradil Aerolizer (Foradil P) with those a non-proprietary single-dose capsule inhaler (ratiopharm), using an 8-stage Andersen Cascade Impactor set at a flow of 60 L/min. Relative to the formoterol ratiopharm capsule inhaler, Foradil Aerolizer produced particles with a smaller mass median aerodynamic diameter (3.5 vs. 4.1 microm, p = 0.018) and a smaller measured particle diameter distribution (geometric standard deviation 2.2 vs. 2.5, p = 0.048). The Foradil Aerolizer produced a 44% higher fine particle dose than the single-dose capsule inhaler (2.6 vs. 1.8 microg, p = 0.0001). Although the single-dose capsule inhaler produced a higher total emitted dose than that from Foradil Aerolizer (11.2 vs. 10.0 microg, p = 0.155, not significant), the respirable fraction from Foradil Aerolizer was 58% higher (25.7 vs. 16.3%, p = 2 x 10(8)). Both devices had a similarly low airflow resistance. These relative particle size profiles suggest that the Aerolizer may provide a more clinically effective delivery of formoterol to the lungs at the high inspiratory flows such as are typically achieved using this device.

Adrenergic beta-Agonists↗
PubMed2006

Intrapulmonary bronchogenic cyst and cerebral gas embolism in an aircraft flight passenger.

Although it is estimated that > 1 billion passengers travel by air worldwide each year, the incidence of in-flight emergencies is low. However, due to nonstandardized reporting requirements for in-flight medical emergencies, the true incidence of pulmonary barotrauma in airplane passengers is unknown. We describe the case of a passenger with an asymptomatic intrapulmonary cyst in whom a severe case of cerebral gas embolism developed during an aircraft flight. The decrease in ambient pressure during the aircraft climb resulted in expansion of the cyst volume based on Boyle's law (pressure x volume = constant). Due to the cyst expansion, we believe tears in the wall led to the leakage of air into the surrounding vessels followed by brain gas emboli. Adult patients with intrapulmonary cysts should be strongly considered for cyst resection or should at least be advised to abstain from activities leading to considerable changes in ambient pressure.

Aged↗
PubMed2006

[Oversized patient arms: a problem with blood pressure measurements].

The increase in the worldwide prevalence of obesity systematically leads to a higher number of individuals who may be wrongly diagnosed as hypertensive because their arms are too large for standard blood pressure cuffs, which are ordinarily appropriate in patients with normal sized arms. The aim was to gain real data of upper arm and wrist circumferences in 327 elected subjects with larger arms (upper arm circumference >32.5 cm) from two Bavarian general practices. We found that 93.9% of all patients had an upper arm circumference of a maximum of 41.0 cm and a wrist circumference of at most 20.5 cm. These data were then compared with the approved size ranges of six wrist blood pressure measurement devices, one special three-in-one cuff for different sizes and the two large adult cuffs recommended by the German Hypertension Society. Availability of one large cuff and one wrist blood measurement device (either used at the upper arm or at the wrist depending on patient dimensions) seems to be sufficient. This should allow for true blood pressure readings to be obtained in at least 96% of all patients with arms of more than normal circumference.

Arm↗
PubMed2005

Spastin related hereditary spastic paraplegia with dysplastic corpus callosum.

Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.

Adenosine Triphosphatases↗
PubMed2005

Frequency of a tau genotype in amyotrophic lateral sclerosis.

We investigated the susceptibility of the dinucleotide polymorphism A0 in the tau gene to amyotrophic lateral sclerosis (ALS). In 416 unrelated patients with ALS and 242 control subjects the A0/A0 genotype was not associated with the pooled sample of ALS cases. Subgroup analysis revealed that in sporadic ALS the A0 polymorphism was significantly overrepresented. There was no association of the A0/A0 genotype with the age and site of disease onset or the presence of dementia. The studied tau genotype may contribute to the multifactorial genetic background of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Changes in indication and results after resection of hepatic metastases from noncolorectal primary tumors: a single-institutional review.

BACKGROUND: The isolated occurrence of noncolorectal liver metastases is rare. The available data are inconsistent in terms of indication for surgery, treatment, and outcome, so a generally applicable therapeutic algorithm is currently lacking. METHODS: A total of 162 patients underwent resection for noncolorectal liver metastases between 1978 and 2001. The patients were divided into two groups from different time periods (group 1, 1978-1989; group 2, 1990-2001) that were similar in terms of number of patients, operating surgeons, and surgical techniques used. The groups were compared, and the data were retrospectively analyzed with regard to indication, survival, and factors predictive for survival. RESULTS: Resection was performed to remove liver metastases from noncolorectal gastrointestinal carcinoma (n = 50), neuroendocrine tumors (n = 12), genitourinary primary tumors (n = 11), breast carcinoma (n = 24), leiomyosarcoma (n = 15), and metastases from other primary cancers (n = 50). Extrahepatic tumor involvement was seen in 38 (23%) of the 162 cases. Sixty-two (38%) major hepatectomies and 100 (62%) minor resections were performed. In 100 (62%) of 162 patients, a curative resection (R0) could be achieved. Overall 2- and 5-year survival rates of 49% and 26%, respectively, were observed, and the median survival was 23 months. Survival was significantly longer in patients who underwent an R0 resection. CONCLUSIONS: In selected patients, resection of noncolorectal liver metastases is associated with a 5-year survival rate of up to 50%. Resection of liver metastases from gastrointestinal adenocarcinomas correlates with a poor prognosis. Extrahepatic metastases may be considered a relative contraindication for liver resection.

Adult↗
PubMed2005

Definition of elective lymphatic target volume in ductal carcinoma of the pancreatic head based on histopathologic analysis.

PURPOSE: In chemoradiation for pancreatic carcinoma three-dimensional target volume definitions could maximize tolerability and therapeutic effect at the same time because toxicity correlates with treatment volume. We aimed to define guidelines for elective treatment of nodal areas based on pathologic nodal involvement to optimize treatment volume for this tumor. METHODS AND MATERIALS: Pathologic patterns of regional nodal spread in 175 patients who underwent primary pancreatoduodenectomy with > or =10 assessed nodes and literature data on para-aortic spread were the base of the definition of the target volume. Significant correlations between spread to lymphatic areas and tumor characteristics were determined using Fisher's exact test. Computed tomography scans and a Pinnacle3 (Philips, Best, The Netherlands) system were used for treatment planning. RESULTS: Among 175 resected tumors without pretreatment, 76% had regional nodal metastasis and 22% had spread to distant nodes. High-risk lymphatic areas were identified and selected for elective treatment. A standardized planning procedure was derived and tested under treatment conditions. CONCLUSIONS: Histopathologic data allowed us to develop recommendations for standardized treatment planning for ductal carcinoma of the pancreatic head. These are proposed for quality assurance in multicenter studies and routine use.

Adult↗
PubMed2005

A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis.

BACKGROUND: Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. METHODS: A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. RESULTS: No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. CONCLUSION: The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality.

Animals↗
PubMed2005

Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD.

A heterozygous R1101K mutation of the p150 subunit of dynactin (DCTN1) is reported in a family with amyotrophic lateral sclerosis (ALS) and co-occurrence of frontotemporal dementia (FTD). Two members of our kindred were affected with motor neuron disease and two with dementia in an autosomal dominant pattern of inheritance. We excluded the involvement of the ALS and FTD-linked genes for copper/zinc superoxide dismutase (SOD1) and tau. The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD.

Amyotrophic Lateral Sclerosis↗