Biomedical subjects

G Heinze

Publications and source records attributed to G Heinze.

At least 37 records · Page 2Linked to original sources

PubMed2001

Analysis of the human progesterone receptor gene polymorphism progins in Austrian ovarian carcinoma patients.

Ovarian carcinoma is the highest death cause in gynecologic malignancies. Although the molecular basis for familial breast and ovarian cancer is elucidated, few genetic markers have been associated with sporadic ovarian carcinoma. A polymorphism in intron G of the human progesterone receptor (PgR), caused by an Alu insertion, was described to be associated with ovarian carcinoma in a pooled German/Irish population. Later on, a G to T substitution in exon 4, causing a Valine to Leucine change in the hinge region of the receptor, and a synonymous C to T substitution in exon 5 were reported to be linked to the Alu insertion. This complex of the PgR gene polymorphism was designated PROGINS. In order to investigate if PROGINS is associated with risk for ovarian cancer in Austrian women, we analyzed DNA from 226 Austrian patients with sporadic ovarian carcinoma and a control group with 194 healthy volunteers for the PROGINS complex. The PROGINS status was studied in association with risk for ovarian carcinoma, the age of the ovarian patients, the protein level of PgR and estrogen receptor (ER) and histopathological parameters. The results indicate that the frequency of PROGINS carriers in Austrian women is similar to those in women in North America and England. There is no significant difference between the PROGINS allele distribution in ovarian carcinoma patients and healthy women. The PROGINS is not associated with increased risk for ovarian carcinomas. Additionally, the protein levels of ER and PgR were independent of the PROGINS status.

Alleles↗

PubMed2001

Femoral neck fracture after removal of the standard gamma interlocking nail: a cadaveric study to determine factors influencing the biomechanical properties of the proximal femur.

We retrospectively analyzed 1334 patients who were implanted standard gamma interlocking nails (SGN) to stabilize trochanteric femoral fractures over the years 1992-1998. Reoperation to remove the nails was performed in 37 patients, in 9 of them purely because of pain. Three out of these 9 patients with removed SGN suffered femoral neck fractures in the early postoperative course after having been mobilized to full weight-bearing capacity. This complication was not observed with other implant systems and, considering the notoriously high complication rate of femoral neck fractures, severely reduces the value of the SGN concept per se. These findings in combination with other known shortcomings of SGNs prompted us to conduct an experimental study on the fracture force of excavated femurs addressing the hypothesis that the specific design of the SGN is responsible for the occurrence of fatigue fractures of the femoral neck. Eighteen matched pairs of fresh human cadaveric proximal femurs, which were treated by insertion and removal of (i) SGNs or (ii) dynamic hip screws (DHS) or (iii) by excavation in the absence of an implant, were subjected to incremental loading cycles and compared to the untreated contralateral femurs. Overall, the fracture force was found to be significantly lower among the treated than among the untreated bones. However, the fracture force required after removal of the DHS system was still significantly higher than for SGN or excavation alone. In this way, our findings demonstrate that removing relatively big implants such as SGN can cause serious complications such as femoral neck fractures. We therefore recommend to leave this type of device in place even after fracture healing except in cases of deep and chronic infection.

Aged↗

PubMed2001

Cytogenetic risk groups in acute myeloblastic leukaemia differ greatly in their semi-solid colony growth.

We have analysed the results of semi-solid bone marrow cultures in 296 patients with de novo acute myeloblastic leukaemia (AML) and correlated them with the leukaemic karyotype. A favourable prognostic karyotype was found in 52 patients (group A, 18.3%), an intermediate karyotype in 163 patients (group B, 57.4%), and unfavourable cytogenetics were observed in 69 patients (group C, 24.3%). Median colony growth according to the three risk groups was 2 (range 0--344) in group A, 14.5 (range 0--5000) in group B and 50.0 (0--3000) in group C (A vs. B, P < 0.001; A vs. C, P < 0.001; B vs. C, P < 0.01). Among the patients treated with chemotherapy (n = 257), median colony growth was 10 (range 0-5000) in those who achieved complete remission (CR) compared with 56.5 (range 0-1000) in patients without remission (NR) (P = 0.002). The median colony growth of all patients [13/10(5) bone marrow mononuclear cells (BMMCs); range 0--5000] significantly discriminated between patients regarding survival (OS 11 vs. 7 months, P = 0.044). However, multiple Cox regression analysis revealed cytogenetic risk groups as the most important predictor for achieving CR, disease-free and overall survival, with colony growth adding no additional prognostic information. In 64 patients, colony growth was also investigated without the addition of exogenous cytokines. Interestingly, none of the patients with a favourable karyotype exhibited autonomous growth, whereas 50% with an intermediate and 73% of patients with an unfavourable karyotype displayed either partial or full autonomous growth in vitro (P = 0.0004). Our data suggest that the growth potential of the leukaemic clone seems to be critically influenced by the molecular changes emerging from chromosomal abnormalities.

Adolescent↗

PubMed2001

Placental expression of cytokeratin 18 and serum levels of tissue polypeptide antigen in women with pregnancy-induced hypertension.

OBJECTIVE: We hypothesized that placental cytokeratin (CK) 18 expression and serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18, are increased among women with pregnancy-induced hypertension (PIH). METHODS: Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched for gestational age and parity, using an immunoradiometric assay. Immunohistochemical detection of CK 18 was assessed in placental specimens of 24 women with PIH and 20 controls. Results were correlated to clinical data. RESULTS: Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of 20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH, respectively (p = 0.008). Median serum levels of TPA in controls and women with PIH were 93.0 U/L (range: 12.5-281.6) and 154.2 U/L (range: 37.3-496.6), respectively (p = 0.001). Serum levels of TPA significantly influenced the odds of presenting with PIH, as well as the odds of developing severe disease (p = 0.003, and p = 0.001, respectively). TPA values were significantly higher among women with severe PIH compared with women with mild PIH and controls, independent of gestational age (p = 0.004). Among women with severe PIH, serum TPA was inversely correlated with fetal birth weight (r = -0.3; p = 0.001) CONCLUSION: Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH. Serum levels of TPA are elevated among women with PIH and correlate with disease severity and low fetal birth weight.

Adult↗

PubMed2001

Carbon monoxide formation in dry soda lime is prolonged at low gas flow.

UNLABELLED: When exposed to volatile anesthetics containing a CHF(2)-group, such as isoflurane, desiccated absorbents produce carbon monoxide (CO). In the anesthesia circuit, the anesthetic flow that passes through the absorber varies with the minute ventilation. We sought to determine CO formation at different levels of test gas flow. Isoflurane 0.5% (series A) or 0.5% isoflurane + 5% CO(2) (series B) in pure O(2) was passed through dry soda lime samples (600 g, Draegersorb 800((R))) at flows of 1, 3, 5, 7, and 10 L/min. Each experiment was performed three times. At the outlet, CO concentration, isoflurane concentration and temperature were continuously recorded. In both series, the duration of CO formation was inversely related to the test gas flow. In series B, mean CO concentrations and the calculated amount of CO formation decreased significantly with increasing flow rates, which was not the case in series A. In both series, the higher the flow rate, the higher was the temperature and the shorter the time until the isoflurane concentration increased to the set level. We conclude that anesthetic degradation in dry soda lime is finite and, as long as no CO(2) is added, will produce roughly the same amount of CO regardless of inflow rate. The inflow rate influences the duration of CO formation such that at lower minute ventilation longer CO formation can be expected. IMPLICATIONS: CO formation from isoflurane degradation in dry soda lime was determined at different rates of test gas flow. The duration and, in the presence of CO(2), the total amount of CO formation were inversely related to the flow rate.

Anesthetics, Inhalation↗

PubMed2001

The standard Gamma nail: a critical analysis of 1,000 cases.

BACKGROUND: The continuous increase in the number of fractures of the proximal femur is directly attributable to the worldwide increase in life expectancy. The standard version of the Gamma Interlocking-Nail (standard Gamma nail [SGN], 200-mm length, 10-degree valgus curvature, two distal locking bolts) was designed because of the demands in orthopedic hip surgery to develop an implant stable enough to mobilize old patients as soon as possible to avoid further morbidity and mortality. METHODS: Between the years 1992 and 1998, 1,000 consecutive patients with peritrochanteric fractures were stabilized by using the SGN and included in this study. Special emphasis was given to the evaluation of the learning curve of the department of traumatology (not of single surgeons) and the influence of prognostic factors on the outcome of such operations. RESULTS: The results of this study show that increasing "department experience" resulted in a reduction of the intraoperative complication rate by a factor of 0.5 (p = 0.0001) per year. This means that even an inhomogeneous mass of 78 surgeons can lower the rate of intraoperative complications by 50% per year because of increased experience. The number of early postoperative complications annually decreased by a factor of 0.8 (p = 0.0042). CONCLUSION: Late postoperative complications correlate negatively with the patient's age (odds ratio, 0.9; p = 0.0001).

Adult↗

PubMed2001

A solution to the problem of monotone likelihood in Cox regression.

The phenomenon of monotone likelihood is observed in the fitting process of a Cox model if the likelihood converges to a finite value while at least one parameter estimate diverges to +/- infinity. Monotone likelihood primarily occurs in small samples with substantial censoring of survival times and several highly predictive covariates. Previous options to deal with monotone likelihood have been unsatisfactory. The solution we suggest is an adaptation of a procedure by Firth (1993, Biometrika 80, 27-38) originally developed to reduce the bias of maximum likelihood estimates. This procedure produces finite parameter estimates by means of penalized maximum likelihood estimation. Corresponding Wald-type tests and confidence intervals are available, but it is shown that penalized likelihood ratio tests and profile penalized likelihood confidence intervals are often preferable. An empirical study of the suggested procedures confirms satisfactory performance of both estimation and inference. The advantage of the procedure over previous options of analysis is finally exemplified in the analysis of a breast cancer study.

Biometry↗

PubMed2001

Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries.

Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

Adrenal Hyperplasia, Congenital↗

PubMed2001

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

Austria↗

PubMed2000

p53 gene status and expression of p53, mdm2, and p21Waf1/Cip1 proteins in colorectal cancer.

Abrogation of the normal p53 pathway is the most common molecular alteration in human cancer. p53 Gene status can be potentially assessed through the expression of proteins known to be activated by the wild-type p53 (wt p53) system, such as mdm2 and p21Waf1/Cip1. In this study, the frequency of mdm2, p21Waf1/Cip1, and p53 protein expression was investigated using immunohistochemistry (IHC) in 88 colorectal carcinomas (CRCs). The relationship between these expressions and p53 status was examined. p53 status and the immunophenotypes characterizing these tumors were correlated with standard prognostic variables. Mutation of p53 was detected using single-strand conformational polymorphism (SSCP) analysis and sequencing. Concordance between p53 gene status and p53 immunoreactivity was seen in 62 of 88 (70.45%) carcinomas. Mdm2 expression was found in 22 of 45 (48.88%) and 5 of 43 (11.62%) of the tumors with wt p53 and mutated p53 (P<0.0001), respectively. Predominantly, higher p21Waf1/Cip1 expression was associated with wt p53 (P<0.001). All wt p53 cases that expressed mdm2 also expressed p21Waf1/Cip1. These results suggest that there is a subgroup of CRCs in which p53 is functionally active, inducing transcription of mdm2 and Waf1/Cip1. Their combined evaluation may provide important clues for planning adjuvant systemic therapy and gene therapy based on the restitution of p53 function. However, no significant association was found between the immunophenotypes and the standard prognostic variables investigated.

Adult↗

PubMed2000

Randomised fellow eye comparison of the effectiveness of dorzolamide and apraclonidine on intraocular pressure following phacoemulsification cataract surgery.

PURPOSE: To compare the effectiveness of 2% dorzolamide and 0.5% apraclonidine on intraocular pressure (IOP) following phacoemulsification cataract surgery. METHODS: This prospective, randomised study comprised 54 eyes of 27 consecutive patients with age-related cataract scheduled for cataract surgery in both eyes. In each patient the eye with the higher degree of cataract was randomly assigned to receive one drop of either dorzolamide or apraclonidine immediately after surgery. The fellow eye was operated on later and received the other treatment. Cataract surgery was performed with a superior 6.0 mm sutureless frown incision, phacoemulsification and implantation of a three-piece PMMA intraocular lens. The IOP was measured pre-operatively as well as 6 h and 20-24 h and 1 week post-operatively. RESULTS: The mean pre-operative IOP was not significantly different between the groups (dorzolamide group, 14.9 +/- 2.3 mmHg; apraclonidine group, 14.6 +/- 2.5 mmHg; p = 0.450). At 6 h post-operatively, the mean IOP was significantly lower in the dorzolamide than in the apraclonidine group (15.6 +/- 3.9 mmHg vs 18.0 +/- 4.0 mmHg; p < 0.001). An IOP increase of more than 5 mmHg at 6 h post-operatively occurred in 3 (12%) eyes in the dorzolamide group and in 9 (36%) eyes in the apraclonidine group (p = 0.034). At 20-24 h post-operatively and at 1 week post-operatively no difference was found between the groups. CONCLUSIONS: 2% Dorzolamide is more effective than 0.5% apraclonidine in preventing the early post-operative IOP increase following phacoemulsification cataract surgery.

Adrenergic alpha-Agonists↗

PubMed2000

Limitations of the transpulmonary indicator dilution method for assessment of preload changes in critically ill patients with reduced left ventricular function.

OBJECTIVE: We examined whether intrathoracic blood volume (ITBV) and total end-diastolic volume (TEDV), determined by the transpulmonary indicator dilution technique, adequately reflect preload changes during fluid administration in patients with reduced left ventricular function. DESIGN: A prospective, controlled, clinical study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: A total of 18 sedated, mechanically ventilated, and moderately hypovolemic intensive care unit patients, eight with reduced left ventricular function (ejection fraction area, 24.9+/-8.0%, group A), ten with normal left ventricular function (ejection fraction area, 57.6+/-13.0%, group B). INTERVENTIONS: Continuous crystalloid infusion over 120 mins at a constant rate of 8 mL/kg/30 mins. MEASUREMENTS AND MAIN RESULTS: Stroke volume index, central venous pressure, pulmonary artery occlusion pressure (PAOP), TEDV, and ITBV were determined simultaneously at baseline and serially every 30 mins during continuous crystalloid infusion. A similar series of measurements was obtained during control conditions. Performance of various variables during fluid administration was assessed by time correlation analysis. Sensitivity for various variables defined as the ability to detect increasing amounts of administered fluid in individual patients was calculated. All examined variables increased during fluid administration and were unaffected during the control period. Mean time correlation (r2) was significantly higher for pressure monitoring (central venous pressure, r2 = 0.8281; PAOP, r2 = 0.5476) than for volume variables (TEDV, r2 = 0.0256; ITBV, r2 = 0.0729) in group A and was high for all variables in group B (central venous pressure, r2 = 0.7056; PAOP, r2 = 0.6241; TEDV, r2 = 0.49; ITBV, r2 = 0.4225). Sensitivities for central venous pressure, PAOP, TEDV, and ITBV after 120 min were 63%, 75%, 25%, and 25% in group A and 90%, 100%, 60%, and 60% in group B, respectively. CONCLUSION: This study demonstrates limitations of the transpulmonary indicator dilution technique for monitoring of intravascular volume in patients with reduced left ventricular function.

Critical Care↗

PubMed1999

Serum concentrations of squamous-cell carcinoma antigen and tissue polypeptide antigen in the follow-up of patients with vulvar cancer.

Our aim was to evaluate the clinical usefulness of serum concentrations of squamous-cell carcinoma antigen (SCC-Ag) and tissue polypeptide antigen (TPA) in the follow-up of patients with vulvar cancer. We measured SCC-Ag and TPA in 480 serum samples of 82 patients with squamous-cell vulvar cancer. Results were correlated with clinical data. SCC-Ag, TPA and the combination of SCC-Ag and TPA reached a sensitivity and specificity of 27%/97%, 28%/75% and 40%/73%, respectively. The sensitivity and specificity of the marker combination SCC-Ag and TPA was not significantly higher compared with SCC-Ag alone (McNemar's test, p = 0.6 and p = 0.09, respectively). Of the 35 patients with recurrent disease during follow-up, 19, 6 and 10 developed local, regional and distant recurrent disease, respectively. SCC-Ag showed lead-time effects in 26%, 75% and 50% and TPA in 25%, 0% and 33% of patients with local, regional and distant recurrent disease, respectively. The combination of SCC-Ag and TPA showed lead-time effects in 50%, 75% and 50% of patients with local, regional and distant recurrent disease, respectively. The difference between median lead-times of the combination of SCC-Ag and TPA and SCC-Ag alone was not statistically significant (Mann-Whitney U-test, p = 0.4). Our data show that serum SCC-Ag displays good sensitivity/specificity characteristics in the follow-up of vulvar cancer patients, with lead-time effects seen in 75% and 50% of patients with regional and distant recurrent disease, respectively. Furthermore, our data indicate that combining SCC-Ag with TPA is not a successful strategy to improve the sensitivity or the duration of lead-time effects in the follow-up of patients with vulvar cancer.

Adult↗

PubMed1999

Prognostic significance of tumor angiogenesis in primary fallopian tube cancer.

Tumor angiogenesis has been found to be prognostically significant in many types of malignant tumors. We assessed tumor vascularity in 43 cases of histologically proven primary fallopian tube cancer, FIGO stage I-IV, using the highly specific endothelial cell marker CD34. Microvessel count was determined by counting CD34-positive cells at 200 x magnification. The 5-year disease-free survival probability was 43.8% (+/- 11.5%) in 24 patients whose tumors had a microvessel count < or = 19 microvessels/field and 19.7% (+/- 9.5%) in the > 19 microvessels/field group (P = 0.046). Stage and microvessel count were statistically significant for disease-free survival in univariate analysis. Therefore, a larger sample size would be required to detect an independent and statistically significant prognostic effect of microvessel density in primary fallopian tube cancer in multivariate analysis.

Adult↗

PubMed1999

The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum.

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.

Abdomen↗

PubMed1999

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients.

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study comprises 86 patients with ovarian cancer, 48 with primary ovarian cancer and 38 with recurrent ovarian cancer, 67 patients with benign ovarian cysts and 42 healthy women. Median serum levels in patients with primary ovarian cancer, recurrent ovarian cancer, benign ovarian cysts and in healthy women were 535.6 (range 129.6-1200) pg ml(-1), 427.3 (range 193.4-1101) pg ml(-1), 371.2 (range 222-986.8) pg ml(-1) and 318.7 (range 241.3-681.4) pg ml(-1) respectively (Mann-Whitney U-test, P < 0.001). Univariate logistic regression models revealed a significant influence of MCP-1 serum levels on the odds of presenting with primary ovarian cancer versus benign cysts and versus healthy women respectively (univariate logistic regression, P < 0.001 and P < 0.001 respectively). In a multivariate logistic regression model considering MCP-1 and CA 125 serum levels simultaneously, both MCP-1 and CA 125 revealed statistical significance on the odds of presenting with primary ovarian cancer versus benign cysts (multivariate logistic regression, P = 0.05 and P < 0.001 respectively). In ovarian cancer patients, MCP-1 serum levels showed a statistically significant correlation with histological grade (Mann-Whitney U-test, P = 0.02) and age at the time of diagnosis (Mann-Whitney U-test, P = 0.03). Elevated MCP-1 serum levels prior to therapy were not associated with disease-free and overall survival (log-rank test, P = 0.2 and P = 0.7 respectively). In summary these data indicate that MCP-1 might play a functional role in the natural history of ovarian cancer and might serve as differentiation marker between benign ovarian cysts and ovarian cancer, providing additional information to the established tumour marker CA 125.

Adult↗

PubMed1999

Fatigue strength of locking screws and prototypes used in small-diameter tibial nails: a biomechanical study.

BACKGROUND: One major problem with the use of small-diameter nails in the treatment of tibial fractures is the high rate of fatigue fractures of the locking screws. The objective of this study was to correlate such parameters as diameter of locking screws, influence of notch effect, and material with fatigue strength and fatigue limit. METHODS: In a biomechanical study, the mechanical properties of 11 different locking screws and screw designs to be used in solid tibial nails were tested under typical fatigue conditions. RESULTS: The results showed that an increase in the screw's diameter significantly increased the fatigue strength of the tested locking screws and prototypes (p < 0.0005). A 20% increase of diameter improved fatigue strength by 25 to 70%. Absence of thread at the location where the screw contacts the nail's aperture (where the main load is transmitted to the screw and where the screw, therefore, usually tends to break) may double the fatigue strength and fatigue limit by avoiding the negative notch effect of the screw's thread. It was further significant that titanium alloys had a higher fatigue strength compared with stainless steel alloys (p < 0.001). However, the fatigue strength of titanium implants is massively reduced by minimal damage to the surface. CONCLUSION: Optimizing the core diameter of the locking screws at the aperture of the solid tibial nail by using screws without a continuous thread generates a fatigue strength two to three times higher compared with screws with a continuous thread. Increasing fatigue strength of locking screws might decrease malunion in fractures stabilized by small-diameter nails.

Biomechanical Phenomena↗

PubMed1999

Wilms' tumour gene (wt1) expression at diagnosis has no prognostic relevance in childhood acute lymphoblastic leukaemia treated by an intensive chemotherapy protocol.

Expression of the Wilms' tumour gene (wt1) has been demonstrated in a large proportion of human acute leukaemias and is thought to play a role in leukaemogenesis. Recent observations in adult patients with acute leukaemia suggest that wt1 gene expression is a poor prognostic factor. In childhood acute leukaemia, the clinical role of wt1 gene expression has not been established. We have therefore investigated bone marrow samples from 50 children with acute lymphocytic leukaemia at the time of diagnosis for the presence of wt1 transcripts to determine whether wt1 gene expression is associated with specific characteristics of leukaemic cells and whether it is predictive of response to treatment. All patients were treated according to the ALL-BFM 90 protocol. The median observation time was 30 months. Wt1 transcripts were detected by RT-PCR in 60% of the diagnostic samples. Wt1 PCR positive patients showed a higher median leukocyte and peripheral blast cell count than wt1 negative patients. High and intermediate risk patients more frequently displayed wt1 transcripts than low risk patients. No correlation between wtl gene expression and FAB type, immunophenotype, co-expression of myeloid antigens or karyotype has been observed. Furthermore, there was no correlation between wt1 gene expression at diagnosis and achievement of complete remission (CR) and no difference in disease-free survival (DFS) or overall survival (OS) between wt1 positive and negative patients (p > 0.1). These data indicate that (1) wt1 gene expression at diagnosis is detected more frequently in patients with high leukocyte and peripheral blast cell counts, but is not associated with specific characteristics of leukaemic cells, (2) wt1 gene expression is not an independent prognostic factor for CR, DFS or OS in childhood ALL treated by an intensive therapy protocol.

Antineoplastic Combined Chemotherapy Protocols↗