Biomedical subjects

P Kolm

Publications and source records attributed to P Kolm.

At least 37 records · Page 2Linked to original sources

PubMed1998

Plasma substance-P and substance-K and gonadal steroids in relation to the gonadotropin surge in normal human reproductive cycles.

PURPOSE: This study was designed to examine changes in peripheral plasma substance-P and -K levels, their association with follicle-stimulating hormone and luteinizing hormone release in normal reproductive cycles in humans, and their correlation with plasma estradiol and progesterone. METHODS: Fourteen healthy, normally menstruating women underwent daily blood sampling (cycle day 4, 4-14 days) for measurement of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone, substances-P and -K, and daily transvaginal ultrasounds assessing follicular growth and documentation of ovulation. RESULTS: Estradiol peaked on day 13, luteinizing hormone and follicle-stimulating hormone peaked on day 14, and progesterone began an exponential increase on about day 13. CONCLUSIONS: In contrast to other experimental designs using in vitro or in vivo rat or monkey tissue, peripheral levels of substances-P (P = 0.8391) and -K (P = 0.3205) reflected no modulation related to midcycle gonadotropin release in cycling woman.

Adult↗

PubMed1998

Analysis of implantation in assisted reproduction through the use of serial human chorionic gonadotropin measurements.

PURPOSE: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels. METHODS: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG10), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG. RESULTS: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups. CONCLUSIONS: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the healthy, successfully implanted conceptus.

Adult↗

PubMed1998

Modified sperm stress test: a simple assay that predicts sperm-related abnormal in-vitro fertilization.

Loss of sperm motility is associated with the process of sperm senescence and occurs at different rates within a given normal or abnormal sperm population. Reactive oxygen species attack cell membrane phospholipids, generating fatty acid peroxides and other degradation products, that also have deleterious effects on sperm motility and fertilizing ability. The objective of this investigation was to study a modification of the original sperm stress test (MOST), changing the culture medium to one offering transitional metals and shortening the total test time, to ascertain whether it can predict fertilization under these laboratory conditions. A total of 41 semen samples was obtained from patients undergoing in-vitro fertilization (IVF) at our institution. Semen samples were grouped into those producing total fertilization rates (FR) within normal limits (>50%) and those showing low total FR (<50%). The normal FR group had a significantly greater MOST mean value than the low FR group (0.71 versus 0.44). Furthermore, there was a statistically significant correlation between the MOST score and ungrouped fertilization rates (r = 0.53, P = 0.0004). Diagnostic statistics for MOST ratio values predicting <50% FR showed an optimal threshold of 0.39. Collectively, sensitivity, specificity, positive predictive value and negative predictive value have their largest values at this threshold. Taking into account the above mentioned threshold figures, there is a significant association between MOST and FR categories (P = 0.0009). In conclusion, MOST is a simple assay that has significant predictive value for sperm related IVF abnormalities.

Adult↗

PubMed1997

Stimulatory effect of a specific substance P antagonist (RPR 100893) of the human NK1 receptor on the estradiol-induced LH and FSH surges in the ovariectomized cynomolgus monkey.

Utilizing a human NK1 receptor antagonist (RPR 100893), the present in vivo study was designed to test the hypothesis that endogenous substance P (SP) modulates the action of 17beta-estradiol in inducing luteinizing hormone (LH) and follicle stimulating hormone (FSH) surges in ovariectomized cynomolgus monkey. Plasma concentrations of LH and FSH as well as NK1 receptor antagonist and SP were measured during the development of the negative and positive feedback phases which follow a single administration of estradiol benzoate (50 microg/kg) to long-term ovariectomized monkeys. Daily administration by gastric intubation of 1 mg/kg or 10 mg/kg of the NK1 receptor antagonist (RPR 100893) leads to detectable levels of the antagonist in the blood of treated animals for at least 6 hr after its administration. These levels are in agreement with the experimentally determined IC50 value of the antagonist. The most striking finding of this study is that LH and FSH releases are enhanced during the descending arm of the estradiol benzoate-induced LH and FSH surges, which suggests that endogenous SP normally has an inhibitory role during this time. The enhancement of LH release is approximately 50%, regardless of the amount of the NK1 antagonist used. However, the enhanced FSH release is more important. Furthermore, blockade of the NK1 receptor with the smaller dose of the antagonist leads to a small, but significant, increase in plasma levels of SP, indicating that blockade of SP receptors leads to an increased release of SP. Collectively, these results further substantiate the link which exists between the ovarian steroid 17beta-estradiol and SP systems. Also, for the first time, these results demonstrate an inhibitory involvement of the human NK1 receptor in the 17beta-estradiol-induced pseudo-ovulatory gonadotropin surges in the ovariectomized monkey.

Animals↗

PubMed1997

Clinical significance of human sperm-zona pellucida binding.

OBJECTIVE: To assess the relationship between sperm morphology and motion parameters and sperm-zona pellucida (ZP) binding capacity under hemizona assay (HZA) conditions and to determine the discriminatory power of the HZA for the prediction of in vitro sperm fertilizing ability. DESIGN: Prospectively designed study. SETTING: Academic tertiary centers. PATIENT(S): One hundred ninety-six couples undergoing IVF therapy participated in this study. INTERVENTION(S): Hemizona assay and IVF results were determined for each couple. MAIN OUTCOME MEASURE(S): Computerized sperm motion analysis, sperm morphology (strict) criteria), and HZA results were correlated with fertilization outcome. RESULT(S): Among sperm parameters from the original ejaculates, morphology was the best predictor of sperm-ZP binding ability; hyperactivated motility was the best predictor of HZA results after swim-up separation of the motile sperm fractions. The HZA index provided the highest discriminatory power for fertilization success/failure, with an overall accuracy of 86%. CONCLUSION(S): Sperm morphology and hyperactivated motility showed a high correlation with the capacity of sperm to achieve tight binding to the ZP. The excellent positive and negative predictive values of the HZA for fertilization outcome provide additional support for the use of this functional bioassay in the decision-making process within the assisted reproduction setting.

Female↗

PubMed1997

ACTH, beta-endorphin, substance P, and corticotrophin releasing hormone in plasma and follicular fluid in hormonally stimulated menstrual cycles for in-vitro fertilization in the human.

Changes in plasma concentrations of ACTH, beta-endorphin (beta-EP) and cortisol have been found to be associated during the human menstrual cycle. Changes in hypothalamic levels of gonadotrophin releasing hormone (GnRH), beta-EP and substance P (SP) have also been associated with the oestrous cycle in the rat. Therefore, an attempt was made to measure the activity of the corticotrophic axis and SP by measuring blood and follicular fluid concentrations of ACTH, beta-EP, SP and corticotrophin releasing hormone (CRH) during the hormonal ovarian stimulation phase for in-vitro fertilization (IVF), in a series of 19 patients. At the plasma level, there was no significant change over treatment days in ACTH (P = 0.1550), beta-EP (P = 0.1137), or SP concentrations (P = 0.5625). CRH was not detectable over treatment days. In addition, there was no significant change in neuropeptide over treatment days between those women who became pregnant and those who did not (P = 0.17 for all). In the follicular fluid, ACTH was not detectable, beta-EP concentration was three times higher than in the plasma, CRH was detectable, and SP concentration was similar to that of plasma. There was no apparent correlation, however, between beta-EP or SP concentrations in the plasma and follicular fluid from a given patient. In conclusion, the absence of changes in the activity of the corticotrophic axis during the hormonal ovarian stimulation suggests that there was no major stress component associated with the stimulation phase of IVF or the occurrence of a pregnancy.

Adrenocorticotropic Hormone↗

PubMed1997

Cryopreservation: a simplified method of evaluation.

A theoretical model is presented by which a true expression of pregnancy rate resulting from stimulated cycles can be calculated. This includes the transfer of both fresh and cryopreserved embryos. It is concluded that the total reproductive potential of a single cycle of stimulation can only be evaluated by including pregnancies arising from all fresh and frozen embryo transfers resulting from that cycle.

Cryopreservation↗

PubMed1996

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation.

PURPOSE: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. METHODS AND MATERIALS: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. RESULTS: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p=0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. CONCLUSION: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas.

Astrocytoma↗

PubMed1996

Detection of air emboli in radiographic contrast media by microwave radiometry.

To evaluate the efficacy of a microwave radiometry system in detecting in-line air emboli in radiographic contrast media, air emboli ranging in volume from 0.1 to 0.005 ml were introduced into ionic (ioxaglate) and nonionic (iohexol) contrast media at 22 or 37 degrees pumped at flow rates of 16.7, 180 or 300 ml/min through polyvinlychloride tubing with an inner diameter of 0.100 inches (2.54 mm) over which was fitted a radiometer antenna connected to a Microwave Medical System F+ radiometer and a computerized data acquisition system. A total of 400 determinations were run, with 10 replicate determinations for each unique set of experimental conditions. The success of air emboli detection was not significantly related to contrast media (p = 0.73) or contrast temperature (p = 0.68). Embolus volume (p < 0.0001) and pump speed (p < 0.0001) were significant factors affecting system performance. The system could reliably detect small (0.005 ml) emboli in both ionic and nonionic low-osmolar contrast media.

Air↗

PubMed1996

p-Glycoprotein expression as a predictor of breast cancer recurrence.

BACKGROUND: Many new prognostic factors for breast cancer have been described, and yet the ability to predict patient outcomes remains poor. Overexpression of p-glycoprotein (p-gp), the multidrug resistance efflux pump, confers a worse prognosis to patients with certain leukemias and other tumors. The purpose of this study was to analyze the potential usefulness of p-gp expression as a prognostic factor in patients with breast cancer. METHODS: Paraffin blocks were obtained from 55 previously untreated patients who underwent surgery between 1987 and 1988. To determine p-gp expression, tumor cell suspensions were incubated with the p-gp-specific C219 monoclonal antibody and analyzed using an indirect immunofluorescent flow cytometric assay. RESULTS: Twenty-four (44%) of the tumors were p-gp positive and 31 (56%) were p-gp negative. Among the p-gp positive patients, 65% had recurrence of their disease, whereas only 13% of the p-gp negative patients experienced recurrence (p = 0.0001). The 5-year disease-free rate for p-gp positive patients was 39% compared with 83% for p-gp negative patients (p = 0.0001). In univariate analysis examining 10 different variables, significant predictors of recurrence were p-gp, stage, and tumor size. Multivariate analysis using Cox Proportional Hazards regression showed that only p-gp and stage were significant independent predictors of recurrence (p = 0.0002). CONCLUSIONS: p-gp is frequently expressed in patients with untreated breast cancer, with p-gp-positive patients being at significantly greater risk for disease recurrence. p-gp appears to be a useful prognostic factor in breast cancer and could potentially help guide management.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Use of a specific zona pellucida (ZP) protein 3 antiserum as a clinical marker for human ZP integrity and function.

OBJECTIVE: To evaluate binding characteristics of a specific zona pellucida (ZP) protein 3 (ZP3) antiserum to human oocytes in order to determine its usefulness as a clinical marker for human ZP integrity and function and its correlation with IVF outcome. DESIGN: Prospectively designed, blinded, internally controlled study. SETTING: Tertiary care academic center. PATIENTS: Patients undergoing IVF therapy who had either total failed fertilization or partial fertilization were studied. INTERVENTIONS: Metaphase II oocytes showing absence of pronuclear formation were salt stored 48 hours after insemination and bisected into matching hemizonae using micromanipulation. One hemizona was incubated with AS ZP3-6 (an antiserum generated against a synthetic ZP3 peptide derived from an amino acid sequence that is highly conserved in the structure of ZP3), whereas the matching hemizona was incubated with AS ZP3-7, an antiserum detecting exclusively mouse ZP3 (internal, negative control). Antibody binding was visualized using the peroxidase-antiperoxidase method and diaminobenzidine as color reagent. RESULTS: A total of 104 unfertilized oocytes were evaluated. Analysis of variance showed a significant interaction between gamete factor groups (sperm and oocyte) and antiserum factor. Patients with oocyte factor had significantly lower mean staining scores for the AS ZP3-6-treated hemizonae than patients with sperm factor. CONCLUSIONS: These results demonstrate that anomalies of human ZP3 can be identified with AS ZP3-6 and that these ZP abnormalities correlate with fertilization failure during IVF treatment. Thus, this newly developed biomarker may be of clinical significance in the identification of oocyte defects that are associated with fertilization disorders and may help in the decision-making process in the IVF-assisted fertilization setting.

Adult↗

PubMed1996

Prenatal ultrasonographic fetal rib length measurement: correlation with gestational age.

The availability of normal data on fetal rib bone length would be of value in a variety of circumstances under which ultrasound examinations are performed. Fetal rib length measurements were obtained in 257 singleton fetuses in a prospective cross-sectional study. The study population consisted of pregnancies between 14 and 40 weeks with no evidence of growth disturbances, or structural or karyotypic abnormalities. Fetal rib length, as a function of gestational age, was expressed by the regression equation: RL = -0.5834 + 0.2030 (GA), where RL is the rib length in centimeters and GA the gestational age in weeks. The correlation was R = 0.94 (p < 0.0001). The normal limits of fetal rib length are defined, and a high correlation between fetal rib length, gestational age, and other standard determinants of fetal growth is demonstrated. Our results indicate that fetal rib length can be a useful adjunct in determining normal fetal growth and in the management of the pregnancy with fetal skeletal dysplasia.

Cross-Sectional Studies↗

PubMed1996

On the interaction of hypnotizability and negative affect in chronic pain. Implications for the somatization of trauma.

The high risk model of threat perception predicts that high hypnotizability is a risk factor for trauma-related somatization. It is hypothesized that high hypnotizability can increase experimentally induced threat or negative affect, as measured by skin conductance level, in a linear or dose-response manner. This hypothesized interaction of hypnotic ability and negative affect was found in a consecutive series of 118 adult patients with chronic pain symptoms. Larger increases in skin conductance levels during cognitive threat were significantly related to higher levels of hypnotizability. In addition, individuals with high hypnotizability retained higher skin conductance levels than individuals with low hypnotizability after stress. The clinical implications of the interaction of hypnotizability and negative affect during threat perception and delayed recovery from threat perception are discussed in terms of cognitive mechanisms in the etiology and therapy of trauma-related dissociative disorders.

Adaptation, Psychological↗

PubMed1996

Treatment and prognosis of primary malignant small bowel tumors.

Primary malignant tumors of the small bowel are a heterogeneous group of tumors and are uncommon compared to tumors in other locations of the gastrointestinal tract. These tumors have been traditionally associated with a poor prognosis. The charts of 53 patients with primary malignant small bowel tumors at major Eastern Virginia Medical School teaching hospitals were retrospectively reviewed. Patient characteristics and presenting symptoms and signs were nonspecific. No single radiographic or endoscopic procedure was performed on every patient, and the diagnosis was suspected preoperatively in only 50 per cent of the patients. Tumors were most common in the ileum, and the most common histologic types were adenocarcinoma (53 per cent) and carcinoid (32 per cent). In univariate analysis, factors determining survival included histologic type, location of tumor, and stage. There was also a trend toward worse survival in patients receiving chemotherapy or radiation therapy, possibly due to patient selection factors. In multivariate analysis, only histology and stage significantly influenced survival. The overall 10-year survival of the entire group was 44 per cent. Small bowel tumors have a variable prognosis. A high index of suspicion and more frequent use of enteroclysis may lead to earlier detection and improved survival.

Actuarial Analysis↗

PubMed1995

Management and prognosis of adenocarcinoma of the appendix.

PURPOSE: Adenocarcinoma of the appendix is a rare neoplasm, and controversies persist regarding management. The purpose of this study was to identify prognostic factors and define management strategies for patients with adenocarcinoma of the appendix. METHODS: A retrospective case series was conducted at three medical school teaching hospitals over a 20-year period from 1972 to 1992. Overall survival was determined by the actuarial life table method. Comparisons of prognostic factors were made using exact nonparametric log-rank tests. RESULTS: Thirteen patients were diagnosed during the study period. Median age was 62 years. There were five males and eight females. The disease was not suspected in any patient preoperatively. Seventy-seven percent of patients had metastatic disease at presentation. Second primary malignancies were found in 15 percent of patients. Thirty-eight percent of female patients had synchronous ovarian lesions. Median survival was 22 months, with an estimated five-year survival of 43 percent (95 percent confidence interval, 22-84 percent). Patients with colonic histology had significantly worse survival than patients with mucinous histology (P = 0.0093). Patients with carcinomatosis had a significantly worse survival than noncarcinomatosis patients (P = 0.0078). Patients who underwent right hemicolectomy had a better prognosis for survival than appendectomy patients, but the difference was not statistically significant. CONCLUSIONS: Carcinoma of the appendix is very difficult to diagnose preoperatively, and most patients are not identified until disease is advanced. Good prognostic factors include mucinous histology and the absence of carcinomatosis. Right hemicolectomy appears to be a reasonable option, although its superiority to appendectomy alone has not been definitively proven. High frequency of ovarian metastases in women suggests a role for bilateral oophorectomy. In addition, a complete work-up of the patient for a synchronous malignancy, especially in the gastrointestinal tract, should be considered.

Adenocarcinoma↗

PubMed1995

Prediction of ovarian response to exogenous gonadotropin stimulation: utilization for collection of primate oocytes for fertilization in vitro.

The predictive value of 2 tests for ovarian response to controlled ovarian hyperstimulation in the cynomolgus monkey model was evaluated. The tests utilized were: 1) the cycle Day 3 (Day 1 = onset of menses) FSH value and 2) the acute estradiol (E(2)) response to a GnRH agonists (GnRHa) administered on Day 3. Both tests were performed during the cycle preceding control ovarian hyperstimulation. Subsequently, monkeys (n = 26) were stimulated with Metrodin(T) (Days 2-6, 25IU/d) and Pergonal(T) (Day 7 to hCG administration, 25IU/d). Laparoscopic oocyte retrieval was performed 32 to 34 after hCG administration. Analysis of the data revealed that Day 3 FSH values could not predict whether an animal would respond well to control ovarian hyperstimulation in a subsequent cycle (P = 0.77). However, the E(2) change 24 h post-GnRHa administration was significantly greater for animals responding well to control ovarian hyperstimulation compared with the animals deleted after 6 d of stimulation (P = 0.042). The mean change in E(2) levels in animals taken to aspiration was 97.8 pg/ml compared with only 21.6 pg/ml for the deleted animals. This differential response of E(2) production after GnRHa treatment was used to correctly identify (by discriminant analysis) 78% of the animals subsequently deleted for poor response. Thus, the increase in serum E(2) level after GnRHa, but not the basal FSH level, was found to be predictive of ovarian response to stimulation in the cynomolgus monkey.

Journal Article↗

PubMed1994

Intratumor variability in prognostic indicators may be the cause of conflicting estimates of patient survival and response to therapy.

The DNA index, percentage of S-phase cells, proliferation fraction, and glutathione (GSH) content were determined at more than 1100 separate sites in 140 human tumors and 140 normal tissues. The study showed that the variability was so great from site to site within a tumor that there was only a 61% chance of identifying an aneuploid tumor clone (when present) if only a single site sample was analyzed for DNA content. Similar broad variability was observed in the percentage of S-phase cells, proliferation fraction, and glutathione content. Since these tumor characteristics are often used to predict the outcome of therapy and patient survival, the inaccuracy and underestimation of the test results may cause conflicting or erroneous predictions. The probability of finding an aneuploid clone or elevated percentage of S-phase cells proliferation fraction and GSH content increased dramatically as the number of sample sites studied per tumor was increased. Statistical analyses indicated that in order to achieve a 90% probability that the test results for these parameters were representative of the whole tumor: (a) all single site testing should be abandoned; (b) assays should be performed on samples taken from 3-7 different sites within each tumor; or (c) samples from each tumor should be pooled and the analyses run on a thoroughly mixed or homogenized aliquot of the multisite sample.

Breast Neoplasms↗

PubMed1994

Ultrasonographic fetal iliac length measurement in the screening for Down syndrome.

OBJECTIVE: Pelvic bone abnormalities are common in newborns with Down syndrome. The aim of this study was to evaluate the utility of ultrasonographic iliac bone length measurement in the identification of fetuses with Down syndrome in the second trimester of gestation. STUDY DESIGN: Ultrasonographic iliac length measurement was obtained, in an axial view of the fetal pelvis, on 10 fetuses with Down syndrome and 180 karyotypically normal fetuses before genetic amniocentesis. Regression equations relating biparietal diameter to iliac length measurement were used to calculate ratios of observed-to-expected length, sensitivity, and specificity at various cutoff points. RESULTS: Linear regression of iliac length measurement on biparietal diameter for normal fetuses resulted in the following equation: iliac length measurement (centimeters) = -0.2723 + 0.0333 biparietal diameter (millimeters). Iliac length measurement in Down syndrome fetuses was significantly longer than in normal controls (p < 0.0001). A ratio of 1.21 for observed-to-expected iliac length measurement yielded a sensitivity of 40%, a specificity of 98%, and positive predictive values of 50% and 2.60%, respectively, in populations at risk for Down syndrome of 1 in 20 and 1 in 750. CONCLUSION: Iliac length measurement is increased in fetuses with Down syndrome. An observed-to-expected iliac length measurement of > or = 1.21 has a positive predictive value of 1/38 in a low-risk population with a false-positive rate of 2%. This preliminary study suggests that iliac length measurement may be useful as an ancillary screening variable in antenatal screening for Down syndrome.

Adult↗