Biomedical subjects

J Hedderich

Publications and source records attributed to J Hedderich.

At least 19 recordsLinked to original sources

PubMed2006

Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or=70 years with advanced ovarian cancer--a study by the AGO OVAR Germany.

BACKGROUND: The purpose of the study was to evaluate first-line platinum/paclitaxel (Taxol) under phase III trial conditions in ovarian cancer (OC) patients aged >or=70 years. PATIENTS AND METHODS: Phase III results of 779 patients with OC International Federation of Gynecology and Obstetrics (FIGO) stage IIB/IV treated with cisplatin/paclitaxel versus carboplatin/paclitaxel were retrospectively analyzed according to feasibility, toxicity (National Cancer Institute Common Toxicity Criteria) and quality of life (QoL) [European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30)] in patients aged <70 or >or=70 years. RESULTS: One hundred and three (13%) patients were aged >or=70 years. Patient characteristics (<70 versus >or=70 years) showed significant differences with regard to Eastern Cooperative Oncology Group performance status, residual disease and constitutional factors but not to FIGO stage, histology or grading. Elderly patients received 98%, 100% and 96% of the recommended paclitaxel, carboplatin and cisplatin dose, respectively, per cycle. Early discontinuation was more frequent in elderly, although QoL, nonhematological and hematological toxicity were comparable between elderly and younger patients, except for febrile neutropenia (5% versus <1%, P = 0.005). There were no significant differences with regard to cycle delays, dose reductions or the use of granulocyte colony-stimulating factor and antibiotics. CONCLUSION: Platinum/paclitaxel appeared to be feasible and tolerable in elderly patients under clinical trial conditions, but there seems to be a different investigators' estimation of toxicity and less intention to maintain trial treatment in elderly.

Adult↗

PubMed2006

Open versus laparoscopic appendicectomy: a critical review.

BACKGROUND: The benefit of laparoscopic appendicectomy remains unclear. We have analysed available randomised studies comparing laparoscopic and open appendicectomy regarding their clinical pitfalls and statistical relevance. METHODS: Thirty eight studies were analysed in terms of the following aspects: A. clinical problems (e.g., expertise of the surgeons, pre- and postoperative antibiotic treatment, definition of complications, blinding of outcomes) and B. statistical problems (e.g., definition of primary and secondary outcomes, power and sample size, statistical methods, confidence intervals, comparability of groups and studies). RESULTS: Most of the studies have clinical and statistical pitfalls. The most important pitfalls are the uncertain expertise of the operating surgeons, blinding, and the exploratory nature of the studies. Our analysis aims at giving useful information for the appraisal of existing studies and the conduct of further studies. It also gives some preliminary results. CONCLUSIONS: More than twenty years after Semm performed the first laparoscopic appendicectomy, it is necessary to clarify the superiority of laparoscopic or open appendectomy with well-defined, carefully designed randomised studies.

Appendectomy↗

PubMed2006

Endothelial and epithelial expression of eotaxin-2 (CCL24) in nasal polyps.

BACKGROUND: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. METHODS: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. RESULTS: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-alpha, INF-gamma, IL-4, or costimulation with TNF-alpha and INF-gamma CCL24 mRNA was significantly enhanced (3.2-19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-alpha, INF-gamma or IL-4 induced CCL24 protein (0.1-0.3 ng/ml) in epithelial cells. Costimulation with TNF-alpha and IL-4 (0.1-30 and 1-30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18-0.31 ng/ml). CONCLUSION: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.

Adolescent↗

PubMed2006

Comparing ultrasound measurements of neonatal hips using the methods of Graf and Terjesen.

In a prospective study, 232 neonates were examined sonographically using the methods of Graf and Terjesen. In order to determine the reproducibility of the methods, 50 hips were evaluated by two skilled examiners. In an inter-observer study, five physicians and five medical students evaluated 24 images, which were evaluated on ten occasions at two-weekly intervals by one of the authors. Statistical evaluation used the Bland-Altman approach. The neonates (110 females, 122 males) were less than four days old. The mean alpha angle was 62.4 degrees and mean femoral head cover was 55.4%. According to Graf's method, 1.3% of hips were pathological, compared with 4.1% according to Terjesen. Spearman's correlation coefficient between femoral head cover and alpha angles was 0.552. The Bland-Altman approach shows greater variation for femoral head cover than for alpha, if measured by experienced examiners. The Bland-Altman approach shows almost equal reproducibility for alpha and femoral head cover in the inter-observer test, but better repeatability for alpha in the intra-observer test. The Graf results relate better than Terjesen's to the well-known frequency of 1% to 2% hip dysplasia in the European population. Kappa statistics indicate a fair agreement between the two methods. Inter-observer evaluation shows an equal reproducibility of both methods, whereas intra-observer tests reveal better repeatability with Graf's method.

Female↗

PubMed2006

[Mutation in factor II and factor V gene in patients with peripheral arterial occlusive disease].

Mutations in factor-V- and factor-II-genes are correlated with an increased risk for venous thrombosis according to the literature. The significance of the mutations in factor- II- and factor-V-genes for the development of the peripheral arterial occlusive disease is not known. Therefore, we investigated the presence of these mutations in 152 patients with documented peripheral arterial occlusive disease and 318 controls without peripheral arterial occlusive disease with polymerase chain reaction (PCR). There was no association between factor-II-mutation and peripheral arterial occlusive disease. The factor-V-mutation, however, was increased in patients with peripheral arterial occlusive disease double fold (12 positive cases in 318 controls, 12 positive cases in 152 patients with peripheral arterial occlusive disease). The significance level was reached (p = 0.05) in statistical analysis but the result did not fall below the significance level as necessary to reach statistical significance (odds ratio 2.19). Nevertheless, from these data we have to discuss a biological relevance of factor-V-mutation in the pathogenesis of peripheral arterial occlusive disease.

Arterial Occlusive Diseases↗

PubMed2005

Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients.

BACKGROUND AND AIMS: Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, clinical penetrance varies and other genes may modify disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n = 56) and C282Y homozygous haemochromatosis patients presenting clinically (n = 60). METHODS: All participating relatives had a structured interview, clinical assessment, and laboratory investigations. Health related quality of life was measured (SF-36 version 2). RESULTS: In total, 92% of 180 eligible first degree relatives were interviewed in the "screened" family group and 85% of 143 eligible relatives in the "patient" group. Of 59 relatives homozygous for C282Y, 76% of men and 32% of women had the "iron phenotype" (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by lifestyle factors, and 6% by being male. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the "screened" and "patient" groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. CONCLUSIONS: HFE C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. Lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes.

Adolescent↗

PubMed2005

Is granulocyte colony-stimulating factor level predictive for human IVF outcome?

BACKGROUND: We investigated granulocyte colony-stimulating factor (G-CSF) in human reproduction. METHODS: From a total sample of 93 patients, we analysed in group 1 (n = 82) the level of G-CSF and estradiol (E(2)) in serum and follicular fluid (FF) on day of follicular puncture (FP). Furthermore, in response to ovarian stimulation, G-CSF levels in serum were compared between low (n = 11), moderate (n = 53) and high (n = 18) response patients. In group 2 (n = 23) serum for G-CSF assessment was collected throughout menstrual cycle until gestation. Group 3 (n = 11) patients with endometriosis were assessed for G-CSF in serum and FF on day of FP without further differentiation. RESULTS: G-CSF in FF was higher than in serum (P < 0.01). G-CSF in serum increased from low through moderate to high response (P < 0.001); pregnancy rates were 0, 24.5 and 33.5% respectively. G-CSF in serum increased throughout stimulation, reached a peak with ovulation induction (P = 0.01) and decreased until embryo transfer (P=0.001). G-CSF level only in pregnant patients (n = 11) increased from embryo transfer to implantation to gestation (P = 0.005). In endometriosis patients G-CSF in serum and FF was lower than in non-endometriosis patients (P < or = 0.03) and corresponded with low response patients. CONCLUSIONS: G-CSF is involved in follicle development and may be a predictor of IVF outcome.

Adult↗

PubMed2005

[Transpalpebral tonometry with a digital tonometer in healthy eyes and after penetrating keratoplasty].

PURPOSE: The Goldmann applanation technique established itself as gold standard for clinical intraocular pressure (IOP) measurement. But the device measures by corneal touch and presupposes corneal conditions within a normal range. So precise determination of IOP is crucial in corneal disorders and after corneal surgery. This pilot study presents tonometry data of normal and postkeratoplasty eyes measured transpalpebrally with a digital tonometer in comparison to Goldmann tonometry. METHOD: The TGDc-01 tonometer is based on a ballistic principle of measurement. IOP was measured in 50 healthy eyes (group 1) and 40 eyes after penetrating keratoplasty (group 2) first by the TGDc-01 and after 3 minutes by Goldmann tonometry (Haag-Streit). Subjective refraction, keratometry and ultrasonic pachymetry were performed in all eyes. The IOP measurements in the postkeratoplasty eyes were done when corneal epithelium was fully closed and only a medium suture edema could be observed. RESULTS: The Pearson's product-moment correlation was r=0,46 for group 1 and 0,65 for group 2. Using the concordance correlation coefficient the value showed a reproducibility index of r(c)=0,44 in group 1 and r(c)=0,60 in group 2. Following the Bland-Altman-analysis 58% of the cases in group 1 had a difference between the two instruments of maximum 3 mmHg. In group 2, 53,5% of the eyes showed an absolute difference between Goldmann and TDGc-01 of 3 mmHg or less. CONCLUSION: A transpalpebral measurement technique-avoiding corneal contact-seems to be an alternative choice in patients with corneal pathologies and after corneal surgery. The TGDc-01 tonometer provided mostly similar results compared to the Goldmann device, but with fluctuations. Keeping the deviations between the two methods in mind we recommend, however, the use of the transpalpebral approach only in combination with other techniques (palpation, indentation) to obtain enough reliability of IOP information in problem eyes.

Data Interpretation, Statistical↗

PubMed2004

Comparable ultrasound measurements of ten anatomical specimens of infant hip joints by the methods of Graf and Terjesen.

PURPOSE: To define which sonographic section planes relative to the acetabular inlet plane will produce analyzable images with the methods of Graf and Terjesen. MATERIAL AND METHODS: Anatomical specimens of infant hip joints were investigated in a water bath using the methods of Graf and Terjesen. Acetabular position was varied in defined increments with respect to the ultrasound beam. The alpha angles and the femoral head coverage (FHC) were measured. RESULTS: To obtain images analyzable by the two methods, the ultrasound beam had to intersect with the acetabular inlet plane at defined angles. The acetabular notch had to be anteriorly rotated from the ultrasound beam plane by at least 20 degrees. Beam entry within a 50 degrees sector posterior to the perpendicular on the inlet plane resulted in analyzable images. The stepwise multiple linear regression analysis showed that alpha angles and FHC were much affected by the coronal-plane transducer tilt. CONCLUSION: The fact that caudal tilts of the transducer are associated with reduced alpha angles and FHC values should be kept in mind in clinical ultrasound investigations. It is recommended that the transducer should be put on the greater trochanter perpendicular to the transverse axis of the body.

Cadaver↗

PubMed2004

Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro.

AIMS: To analyse the expression of alphavbeta6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. METHODS AND RESULTS: A new monoclonal antibody to the human beta6 subunit, 5C4, was used to locate alphavbeta6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alphavbeta6 extracted from histological sections. Alphavbeta6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alphavbeta6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta6 than poorly differentiated tumours. Peritumoral epithelial tissues where alphavbeta6-expressing tumours arose also expressed alphavbeta6. There was no correlation between expression of alphavbeta6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alphavbeta6 up-regulation, but appeared independent of classical ligand binding to alphavbeta6. CONCLUSIONS: Our findings indicate that: (i) alphavbeta6 is overexpressed in pancreatic adenocarcinomas; (ii) alphavbeta6-positive carcinomas originate from alphavbeta6-expressing tissues; (iii) alphavbeta6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alphavbeta6 in pancreatic carcinoma cell lines accompanies spheroid formation.

Adenocarcinoma↗

PubMed2003

Collagen crosslink excretion and staging of oral cancer.

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

Adult↗

PubMed2003

[In-vitro comparison of the effectiveness of different high-speed rotatory catheters].

OBJECTIVE: To determine the in vitro effectiveness of the Amplatz and Rotarex catheters for thrombus fragmentation and combined thrombus fragmentation and aspiration. MATERIALS AND METHODS: Clots (n = 100) from 5-day-old porcine blood (8.5 g) were fragmented with the 8F Rotarex trade mark catheter (RR; 40.000 rpm), which was directed with or without a coaxial guide wire (GW 0.020 inch [8 F RR(GW)], GW 0.014 inch [6 F RR(GW)]), and with the 7 F Amplatz catheter (ATD; 150.000 rpm), in an artery flow model (pulsed flow of 700 ml/min) simulating the superficial femoral artery. To increase the wall adherence of the thrombus, an additional equal number of silicon tubes (with an inner diameter of 7 mm) were fitted inside with a metallic mesh (wall-adherent thrombus [WAT]; 6 F RR(WAT), 8 F RR(WAT), 6 F R(WAT-GW), 8 F RR(WAT-GW), ATD(WAT) ). The effluent was passed through a three-step filter system (10 to 1000 micro m; pressure gradient 35 mmHg). RESULTS: Highest effectiveness was found for 8 F RR (no remaining thrombus detectable) compared to 6 F RR (0.08 g) and ATD (0.07 g), with a p < 0.001 for both methods. The aspirated volume was significantly lower when 6 F and 8 F RR were used with a coaxial guide wire (p < 0.001). The total emboli rate for 8 F RR was significantly lower compared to ATD (p < 0.001). Even when working without a guide wire, 8 F RR caused the lowest proportion of emboli (depending on the modification 0.12 % to 1.76 %; compared to all p < 0.05). Emboli rates reached 7.99 % for 6 F RR (compared to all p < 0.001) and were maximal 5.61 % for ATD. CONCLUSIONS: The tested mechanical thrombectomy catheters have a high potential for in vitro thrombectomy with moderate performance differences. In contrast to the guidewire-directed Rotarex fragmentation-aspiration device, the ATD trade mark fragmentation catheter and prototype Rotarex 6 F catheter have a considerable peripheral embolization rate of particles larger than 1000 micro m, probably requiring additional measures for in vivo thrombectomy.

Animals↗

PubMed2002

Concentration of collagen cross-links in human dentin bears no relation to the individual age.

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen cross-link residues. HP is present in most tissues, whereas LP is specific for bone and dentin. Based on the current literature there are certain indications that measurement of the concentrations of HP and LP in dentin may be a valuable tool to determine the individual age. The purpose of this investigation was to assess if the concentrations of LP and HP in dentin increase during lifetime. We have investigated 173 molars from 173 individuals (2 through 78 years of age, 31 primary and 142 secondary teeth) in the course of the present study. Levels of LP and HP were measured by HPLC and fluorescence detection. The results show that dentinal concentrations of HP and LP did not increase with age and varied between individuals of the same age and that determination of dentinal concentrations of HP and LP cannot be used to determine the individual age.

Adolescent↗

PubMed2002

Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei.

The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.

Adult↗

PubMed2002

Long-term results after surgical correction of atrioventricular septal defects.

OBJECTIVE: Review of the results of surgical correction of atrioventricular septal defects (AVSD), identification of risk factors for mortality and failure of left AV valve repair and determination of the impact of cleft closure on postoperative AV valve function. METHODS: Between 1975 and 1995, 121 consecutive patients (55 males, 66 females) underwent surgery for biventricular correction of AVSD with a median age of 1.2 years and a median weight of 7.6 kg. Sixty-five patients had a complete AVSD, 17 patients an intermediate type, and 39 patients a partial AVSD. The left AV valve (MV) cleft was closed in 53 patients (43.8%). The mean follow-up time is 7.2+/-4.6 years. RESULTS: Actuarial survival of the whole group after 1 year was 80%, after 10 and 20 years 78 and 65%, respectively. There were 18 early deaths (7-day mortality, 10.7%; 30-day mortality, 14.9%) and eight late deaths. In a univariate analysis, risk factors for early or late death were diagnosis of complete AVSD (P=0.006), no cleft closure (P=0.024), postoperative complications (P<0.0001), age <1.2 years (P=0.017), weight <7.6 kg (P=0.002), PA/Ao pressure ratio >0.7 (P<0.0001), and ECC time >110 min (P=0.002). In the multivariate analysis, postoperative complications (P=0.003) and PA/Ao pressure ratio >0.7 (P=0.001) had parallel effects on the postoperative risk for mortality. Moderate or severe MV regurgitation was present in six patients (6.0%) in the first evaluation after discharge and in 20 patients (20.4%) in the most recent postoperative control. There were 25 reoperations in 17 patients, of which 15 had to be performed for MV regurgitation and two for MV stenosis. Freedom from reoperation was 91% at 1 year, 79% at 10 years, and 76% at 15 and 20 years. We could not identify a statistically significant risk factor for reoperation. CONCLUSIONS: In patients with AVSD of various morphologies closure of the left AV valve cleft significantly improves outcome without affecting the need for reoperation. Risk factors for early and late death (multivariate analysis) were a pulmonary/aortic pressure ratio >0.7 and the occurrence of any complication after surgery. The concept of an early surgical AVSD correction before an increase in pulmonary vascular resistance and AV valve deformations occur would represent a better surgical option than a late correction as done in our series. Early correction allows for reduction of early mortality, superior long-term survival rates and a high freedom from subsequent valve degeneration.

Actuarial Analysis↗

PubMed2001

Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation.

BACKGROUND: In the current study the authors attempted to evaluate genetic alterations in a large set of primary ovarian carcinomas and to compare the genetic findings with clinical parameters such as grade of tumor differentiation. This strategy was applied to identify chromosomal regions containing genes associated with tumor progression. METHODS: Genetic imbalances were assessed in 106 primary ovarian carcinomas using comparative genomic hybridization (CGH). CGH was applied because it is a powerful tool with which to screen the entire genome of a tumor for genetic changes by highlighting regions of altered DNA sequence copy numbers (deletions and amplifications). Multivariate statistical standard procedures were used to determine an association between tumor grading and genetic alterations. RESULTS: One hundred three carcinomas showed aberrant CGH profiles. The most frequent alterations were amplifications of 8q, 1q, 20q, 3q, and 19p, which occurred in 69-53% of tumors, and underrepresentations of 13q, 4q, and 18q, which occurred in 54-50% of tumors. Undifferentiated ovarian carcinomas (World Health Organization Grade 3) were found to be correlated significantly with underrepresentation of 11p and 13q as well as with overrepresentation of 8q and 7p (P = 0.001, 0.001, 0.01, and 0.027, respectively). However, 12p underrepresentation and 18p overrepresentation were significantly more frequent in well and moderately differentiated tumors (P = 0.01 and 0.004, respectively). To facilitate the interpretation and clinical application of the results of the current study, the significant aberrations were translated into a score system. This score system can be used easily for the prediction of an undifferentiated phenotype with a specificity and sensitivity of 79% and 86%, respectively. CONCLUSIONS: The current study data show that primary ovarian carcinomas are based on consistent genetic alterations that most likely are important for the development of this tumor entity. The correlation between certain aberrations and undifferentiated carcinomas may help to discriminate between primary and secondary genetic events and may indicate the location of those genes involved in cellular functions associated with tumor progression and the development of anaplastic and aggressive phenotypes.

Cell Differentiation↗

PubMed2001

Tetralogy of Fallot: influence of surgical technique on survival and reoperation rate.

BACKGROUND: The influence of different surgical techniques in patients with Tetralogy of Fallot (TOF) on long-term survival and reoperation rate is still a matter of controversy. PATIENTS AND METHODS: The data of 266 patients (152 male, 114 female, mean body weight: 13.4 +/- 11.9 kg, mean age 4.1 +/- 6.0 years) with TOF, including 30 patients (11.2 %) with TOF/pulmonary atresia, were analyzed retrospectively. A palliative surgical procedure preceded definite correction between 1975 and 1999 in 46 patients (17.5 %). The surgical technique consisted of a transannular patch in 103 patients (40.1 %); in 133 patients (51.8 %), a non-transvalvular technique was used. In 33 patients (12.3 %), a conduit was implanted into the right ventricular outflow tract (RVOT). For surgical access to the cardiac defects, a transventricular approach was used in 138 patients, and a transatrial/trans-pulmonary approach in 26 patients. The mean follow-up time of all patients was 6.6 years. RESULTS: Kaplan-Meier survival for the entire group was 86.2 % at one year and remained stable at 85.6 % after 5 years. The 30-day mortality was 10.1 % (27 patients). Fatal risk factors were: previous cardiac surgery, preoperative oxygen saturation (SO(2)) < 80 %, diagnosis of pulmonary atresia, prolonged aortic clamping or bypass time, postoperative infections, and early revisions. Freedom from reoperation was 91.6 % after 5, 84.5 % after 10, and 52.6 % after 20 years. There was no correlation between the different surgical techniques (transannular patch, non-transvalvular techniques, transventricular approach) applied and the mortality or the rate of reoperations. CONCLUSIONS: In our series of TOF patients operated over a period of 25 years, we were unable to assess an influence of the surgical technique used for definite correction on mortality or reoperation rate. Pulmonary atresia in patients with TOF is associated with a higher risk of death and reoperation.

Adolescent↗

PubMed2001

Interaction of interleukin-6 on human granulosa cell steroid secretion.

Numerous studies have shown that a variety of cytokines are involved in the regulation of ovarian function. Interleukin-6 (IL-6), has been found in follicular fluid. In this report we show by immunocytochemical methods the localization of the extracellular domain of the IL-6-receptor and its associated signal transducer glycoprotein gp 130 on the surface of granulosa cells (GCs). The possibility that IL-6 may also influence the basal and FSH-stimulated production of estradiol (E2) and progesterone (Prog) by GCs in vitro was also investigated. GCs were obtained from infertile patients undergoing in vitro fertilization and embryo transfer treatment and cultured for 72 h or were given increasing concentrations of human recombinant IL-6 (8--128 pg/ml) in the absence or presence of FSH (96 U/ml). For the time-course studies, FSH-stimulated GCs were treated in the absence or presence of IL-6 (128 pg/ml) and supernatants were assayed at 24 h intervals (24-96 h) for E2 and Prog productions. The results show that increasing amounts of IL-6 significantly inhibit E2 production in the absence or presence of FSH vs untreated controls (P=0.025 at IL-6=128 pg/ml and P=0.016 at IL-6=16 pg/ml respectively). IL-6 also inhibited FSH-stimulated but not unstimulated Prog release (P=0.038 at IL-6=8 pg/ml). These findings suggest that IL-6 may be one of the factors that plays a local regulatory role in the course of FSH-stimulated E2 and Prog release. The time-course studies of the effect of the absence or presence of IL-6 demonstrated a significant inhibitory effect on both E2 and Prog secretion (P<0.001) by FSH-stimulated GCs. As infections of the female reproductive tract are often accompanied by elevated local IL-6 levels, this factor may be one of the links leading to endocrine reproductive dysfunction during genital infections.

Cells, Cultured↗