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Biomedical subjects

C Fabian

Publications and source records attributed to C Fabian.

At least 19 recordsLinked to original sources
PubMed2005

Shakeup excitation during optical tunnel ionization.

Shakeup of a two-electron system is investigated in the strong infrared laser field limit, both theoretically and experimentally. During tunnel ionization the electron shakes up a second electron to an excited bound state. Theoretically, a complete analytical theory of shakeup in intense laser fields is developed. We predict that shakeup produces one excited sigma(u) D(+)(2) state in approximately 10(5) ionization events. Shakeup is measured experimentally by using the molecular clock provided by the internuclear motion. The number of measured events is found to be in excellent agreement with theory.

Journal Article↗
PubMed2004

Influence of sex, estrous cycle and motherhood on dendritic spine density in the rat medial amygdala revealed by the Golgi method.

The medial nucleus of the amygdala (MeA), a sexually dimorphic area, contains estrogen and androgen receptors and has an integrative role in behavioral, vegetative and endocrine activities of rats. The density of dendritic spines along the first 40 microm of dendritic length was studied in neurons from the anterodorsal (MeAD), posterodorsal (MePD) and posteroventral (MePV) aspects of the MeA in males, in virgin females during the four phases of the estrous cycle and in multiparous females in diestrus. The single-section Golgi method was employed (N=48 observations per experimental group). In the three MeA subnuclei males showed more dendritic spines than virgin females (P<0.001), with the only exception being the MePD data of females in diestrus (P>0.05). In virgin females, whereas more dendritic spines were found in diestrus, a decline in these values was found during the proestrus, estrus and metaestrus in the MePD and MePV (P<0.05) but not in the MeAD (P>0.05). Compared with virgin females in diestrus, postpartum rats showed more spines in the MeAD (P<0.001) and fewer in the MePD (P<0.001) but no difference was found in the MePV (P>0.05). These data suggest that there are subregion-specific differences in the density of dendritic spines within the MeA and that they appear to be affected by sex, cyclic fluctuations in the levels of ovarian steroids and following pregnancy in rats. These findings may add to the understanding of the MeA neuronal plastic changes that affect the ongoing processing of sensory information and the organization of the neuroendocrine and behavioral basis of reproduction.

Amygdala↗
PubMed1999

Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control?

Two separate trials compared controlled-release (CR) oral oxycodone (administered every 12 hours) with immediate-release (IR) oxycodone (4 times a day) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation. In one study, 48 patients with cancer pain were randomized to open-label titration with either CR or IR oxycodone (maximum dose, 400 mg/day) for a period of up to 21 days. In a study of similar design, 57 patients with low back pain were titrated with either CR or IR oxycodone (maximum dose, 80 mg/day) for a period of up to 10 days. The majority of patients in both studies were converted to oxycodone from other opioid analgesics. Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control, the time to achieve stable pain control, and the degree of pain control achieved. Among cancer patients, 85% achieved stable analgesia, 92% with the CR formulation and 79% with the IR formulation. Among noncancer patients, 91% achieved stable pain control, 87% with the CR formulation and 96% with the IR formulation. The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids: nausea, vomiting, constipation, somnolence, dizziness, and pruritus. Nausea and vomiting were the most frequently cited reasons for treatment discontinuations. These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic, moderate to severe pain.

Adult↗
PubMed1998

[Bone density of spongiosa and cortical bone of the lumbar spine. Relations to sex, age and spinal deformities in a regional collective of the European Study of Vertebral Osteoporosis (EVOS)].

BACKGROUND AND METHOD: In an additional bone density measurement protocol to the European Vertebral Osteoporosis Study (EVOS) separate spongious and cortical density measurements (sQCT) were carried out at the first 3 lumbar vertebrae in 293 volunteers (92 men and 201 women) in 3 Berlin regional centers. RESULTS: The spongious mineral density decreases from proximal to distal (L1 to L3), the cortical density increases from proximal to distal, mainly in men. Men showed no significant decrease of cortical density and a lower decrease of spongious density with age compared to women. A comparison of bone mineral density with vertebral height indices of McCloskey/Kanis, Eastell/Melton and Felsenberg showed significant differences of spongious density between a group with normal vertebral height and a group with at least one pathologically degraded vertebra. Individuals with osteoporosis according to the WHO-definition showed a higher prevalence of vertebral deformities. No significant loss of cortical density was observed in these people.

Age Factors↗
PubMed1996

The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio.

In a large-scale screen, we isolated mutants displaying a specific visible phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were mutagenized with ethylnitrosourea (ENU) and F2 families of single pair matings between sibling F1 fish, heterozygous for a mutagenized genome, were raised. Egg lays were obtained from several crosses between F2 siblings, resulting in scoring of 3857 mutagenized genomes. F3 progeny were scored at the second, third and sixth day of development, using a stereomicroscope. In a subsequent screen, fixed embryos were analyzed for correct retinotectal projection. A total of 4264 mutants were identified. Two thirds of the mutants displaying rather general abnormalities were eventually discarded. We kept and characterized 1163 mutants. In complementation crosses performed between mutants with similar phenotypes, 894 mutants have been assigned to 372 genes. The average allele frequency is 2.4. We identified genes involved in early development, notochord, brain, spinal cord, somites, muscles, heart, circulation, blood, skin, fin, eye, otic vesicle, jaw and branchial arches, pigment pattern, pigment formation, gut, liver, motility and touch response. Our collection contains alleles of almost all previously described zebrafish mutants. From the allele frequencies and other considerations we estimate that the 372 genes defined by the mutants probably represent more than half of all genes that could have been discovered using the criteria of our screen. Here we give an overview of the spectrum of mutant phenotypes obtained, and discuss the limits and the potentials of a genetic saturation screen in the zebrafish.

Animals↗
PubMed1996

Patterns of recurrence for advanced colon cancer modified by whole abdominal radiation and chemotherapy.

Abdominal failure for colonic carcinoma patients following curative resection has been high in patients with advanced disease stage, particularly when increased numbers of lymph nodes are involved. Surgeons desire curative treatment for their patients, but they interpret local and regional lymph node recurrence as a failure of surgical resection. The effect of current adjuvant treatment protocols on modifying patterns of relapse, particularly in the abdomen, has not been well studied and is of interest to surgeons. We analyzed reported patterns of failure of patients with Stage C2 colon cancer from two colon cancer adjuvant treatment studies; 5-FU plus levamisole (SWOG 8591) and 5-FU, whole-abdominal radiation, and tumor boost. The total number of recurrences in SWOG 8591 at all sites was reduced. The percent of lung relapses was reduced from 34 per cent to 20 per cent in the treatment group, but the percentage of local relapse increased from 20 per cent in the observation group to 27 per cent in the 5-FU plus levamisole group. Similarly, the number of first relapses was fewer at a local site in the 5-FU plus levamisole group, but the percent of relapses at the local site was not reduced (18 vs. 22%). Advanced C2 patients who received regional treatment on 5FU and whole-abdominal radiation produced the lowest percent of local relapse (12%), suggesting a benefit for regional treatment. Further study of patterns of relapse after resection and adjuvant treatment in high risk C2 patients may lead to further progress in control of advanced, curative colon carcinoma.

Adjuvants, Immunologic↗
PubMed1995

Adjuvant continuous infusion 5-FU, whole-abdominal radiation, and tumor bed boost in high-risk stage III colon carcinoma: a Southwest Oncology Group Pilot study.

PURPOSE: Results of a combined modality adjuvant pilot program of low-dose continuous-infusion 5-fluorouracil, whole-abdominal radiation, and tumor bed boost in patients with colon cancer with involved nodes and serosal involvement are presented. METHODS AND MATERIALS: Forty-one eligible patients with completely resected T3N1-2M0 colon cancer (modified Astler-Coller C2) were treated with 5-fluorouracil (5-FU) at a dose of 200 mg/m2/day by continuous infusion and 30 Gy of concomitant whole-abdominal radiation in 1 Gy fractions. An additional 16 Gy boost to the tumor bed was administered in 1.6 Gy fractions. After completion of combined modality treatment and a 21-day rest period, patients received 4 days of 5-FU at a dose of 1000 mg/m2 by continuous infusion every 28 days for nine cycles. RESULTS: Five-year disease-free and overall survival estimates were 58 and 67%, respectively, for all T3N1-2 patients. Five-year disease-free and overall survival estimates for the 19 patients with four or fewer nodes were both 61%. Five-year disease-free survival and overall survival estimates for the 20 patients with more than four involved nodes were 55% and 74%, respectively (the exact number of involved nodes were unknown for two patients). Disease-free and overall survival estimates for patients treated with 5-FU and radiation compare favorably to the 5-FU plus levamisole arm of the intergroup adjuvant colon study (Int 0035/SWOG 8591) in patients with more than four positive nodes where the 5-year disease-free and overall survival estimates were 35% and 39%, respectively. Disease-free and overall survival estimates for patients with four or fewer nodes in the 5-FU plus levamisole arm of the intergroup study were 64 and 68%, which is not markedly different from results obtained with radiation and 5-FU in the current study. There were no treatment-related fatalities. Seventeen percent of patients had severe and 7% had life-threatening toxicity of any kind. One patient had an acute partial bowel obstruction and two patients had chronic low grade enteritis. CONCLUSION: Continuous infusion 5-FU and whole-abdominal radiation with tumor bed boost should be further investigated in a larger trial of T3N1-2 colon cancer.

Adult↗
PubMed1993

Phase II trial of ifosfamide and cisplatin in the treatment of metastatic sarcomas: a Southwest Oncology Group study.

The Southwest Oncology Group (SWOG) performed a phase II trial of a combination of ifosfamide/mesna/cisplatin in patients with metastatic soft-tissue sarcoma who had previously received one chemotherapeutic regimen. A total of 39 patients were registered in the study, including 7 treated during a limited-institution pilot phase; 38 patients were fully eligible and evaluable. During the pilot phase, patients were treated with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on days 2 and 9. Due to excessive myelosuppression, the day-9 cisplatin dose was dropped when the study was opened groupwide, and the subsequent 32 patients were treated at 3- to 4-week intervals with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on day 2. Myelosuppression was severe, with granulocytopenia (< 0.5 x 10(9)/l) being observed in 26 of 38 patients. Three cases of National Cancer Institute grade 3 or 4 nephrotoxicity (serum creatinine, > 3 times the normal value) and three cases of grade 3 or 4 central nervous system toxicity were reported. Overall, three complete and five partial responses were achieved, for a major response rate of 21%. The median survival of all patients was 11 months. We conclude that ifosfamide-based chemotherapy can produce objective responses in previously treated patients with metastatic soft-tissue sarcoma but that cisplatin increases the toxicity of therapy. Phase II trials of new agents are needed to identify drugs with clinical activity in the treatment of soft-tissue sarcomas.

Adolescent↗
PubMed1992

Poland anomaly with a limb body wall disruption defect: case report and review.

We describe a female infant with apparent Poland anomaly (PA) and limb body wall defect. Analysis of the defects suggest that a disruption of the lateral embryonic plate mesoderm may have been responsible for the observed lesions. Because of the overlap of this case with PA, we re-examined previous reports of this syndrome. We think that the lesions could be equally well explained as a mesodermal disruption, and point out a previously unrecognised discrepancy between sex and affected side in sporadic PA and inherited PA which supports this view.

Diaphragmatic Eventration↗
PubMed1992

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.

Aged↗
PubMed1991

Effect of starch malabsorption on fecal bile acids and neutral sterols in humans: possible implications for colonic carcinogenesis.

Epidemiological and experimental studies indicate a strong association between an elevated colon cancer risk and increased fecal excretion of secondary bile acids, neutral sterols, and prolonged gastrointestinal transit time. Starch malabsorption, on the other hand, has been reported to be a possible protective factor in colon carcinogenesis. To study the impact of starch malabsorption on these parameters, 12 healthy volunteers consumed a diet rich in starch for two 4-week periods. During a double-blind crossover trial they received the alpha-glucosidase inhibitor acarbose (BAY g 5421) in one of the study periods and placebo in the other. During acarbose treatment stool wet weight increased by 68%, stool dry weight by 57%, and gastrointestinal mean transit time by 30%. Fecal concentrations (mg/g dry weight) of the neutral sterols coprostanol, coprostanone, campesterol, 4-cholesten-3-one, and beta-sitosterol decreased by 36.8, 48.7, 42.1, 34.6, and 39.4%, respectively, under acarbose. Concentrations of the major secondary bile acids, deoxycholic and lithocholic acid, decreased by 59.9 and 52.2%, respectively. In spite of an increased stool weight, also daily excretion (mg/day) of these two bile acids was lower under acarbose (47.9 and 36.6%, respectively) compared to placebo, whereas excretion of the main primary bile acid, cholic acid, rose from 22.58 mg/day to 379.80 mg/day during the acarbose period. The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development.

Acarbose↗
PubMed1991

Reversal of multidrug resistance in HL-60 cells by verapamil and liposome-encapsulated doxorubicin.

The means of circumventing multidrug resistance was investigated in HL-60 and HL-60R (a drug resistance variant) cell lines. The HL-60R cell line was developed from the parent line by serial exposure to increasing concentrations of doxorubicin over a 4-month period. This drug resistant cell line expressed P-glycoprotein in its cell surface and is 80-fold more resistant than the parent cell line. Multidrug resistance, as evaluated by a cell cytotoxicity assay using doxorubicin, can be overcome by use of verapamil. Multidrug resistance can also be circumvented when doxorubicin is encapsulated in liposomes. The combination of verapamil and doxorubicin-encapsulated liposomes does enhance circumvention of multidrug resistance beyond the effect of each agent alone, implying a synergistic effect. The lipid composition of the liposomes does affect the rate of drug uptake but not the overall cytotoxic effect of doxorubicin. The synergistic reversal of multidrug resistance by doxorubicin-encapsulated liposomes and verapamil suggests a multifactorial basis for drug resistance in this cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin's disease. A Southwest Oncology Group study.

The authors reviewed the records of 139 patients who had laparotomy plus computed tomography (CT) and/or lymphangiograms (LAG) as part of a their staging workup for Hodgkin's disease, in accordance with Southwest Oncology Group (SWOG) protocol 7808. They evaluated the relative ability of CT and LAG to detect disease in the abdomen. Two regions of the abdomen were designated, the upper and the lower, to further examine the capabilities of CT and LAG in the lower abdomen and CT in the upper abdomen. A LAG was more sensitive (P less than 0.05) than CT in detecting positive lower abdominal nodes. In the upper abdomen, CT scan had low sensitivity for detecting positive nodes, liver, or spleen. This study suggests that LAG of the lower abdomen provided more information than CT, and therefore should not be abandoned as a valid method for detecting nodal disease.

Abdomen↗