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Biomedical subjects

C Christensen

Publications and source records attributed to C Christensen.

At least 19 recordsLinked to original sources

Paclitaxel-induced apoptosis in MCF-7 breast-cancer cells.

A study of MCF-7 human breast cancer cells was undertaken to ascertain the degree of apoptosis induction by paclitaxel and if the induction of apoptosis could be enhanced by caffeine. Paclitaxel (0-20 ng/ml) caused concentration-dependent increases in morphologically identifiable apoptotic cells (up to 43% of cell population) and cells with DNA strand breaks (up to 38%), a commonly cited marker of apoptosis. Maximal DNA strand breakage occurred after 16 hr of exposure to paclitaxel and maximal apoptotic-appearing cells occurred after 24 hr. The remaining non-apoptotic paclitaxel-exposed cells were growth arrested in G2. A 4-hr exposure to caffeine concentration-dependently (0-20 mM) increased apoptosis to 88% of the cell population. Our results show induction of apoptosis in breast cancer cells by paclitaxel, and enhancement of this process by caffeine.

Adenocarcinoma

Multifractionated high-dose-rate brachytherapy with concomitant daily teletherapy for cervical cancer.

BACKGROUND: High-dose-rate (HDR) brachytherapy has been the preferred treatment for cervical cancer at Wayne State University since 1987. The outcome of the first 105 patients treated is analyzed. PURPOSE: To determine clinical efficacy of the HDR modality. METHODS: We reviewed 105 patients and evaluated the 88 patients treated for cervical carcinoma with HDR and external beam radiotherapy (EBRT) from August 1987 to December 1992. Patients received initial external radiation to the pelvis (total dose of 19.8 to 39.6 Gy in 11 to 22 fractions), followed by outpatient HDR brachytherapy (3 fractions/week, 386 cGy/fraction to Point A, total of 8 to 12 fractions) and concurrent daily EBRT (1.8 to 2.0 Gy) to lateral parametria. During the HDR period of treatment, step wedge transmission blocks were used to shield central pelvic tissue while treating peripheral pelvic tissues with EBRT. Patient distributions were as follows: 25, IB/IIA; 35, IIB/IIIA; and 28, IIIB/IVA. There were 56 African American and 32 Caucasian patients with mean age of 55 (range 19-89). The median follow-up was 33 months (range 20 to 76 months). Kaplan-Meier analysis was performed. RESULTS: Three-year survival rates were 88%, IB/IIA; 69%, IIB/IIIA; 56%, IIIB/IVA; and 72% overall. Local control was achieved in 71/88 (80%) of patients. Failure site was cervix or within the pelvis in 12 patients, distant metastasis only 17 patients, and combined local and distant in 5 patients. Of the failures, 82% (28/34) died within 2 years. There were 3 grade III/complications (3.4%). CONCLUSION: Results compare favorably with previous LDR experience.

Adult

Diagnosing groups: charting the flow of information in medical decision-making teams.

Several hypotheses derived from an information sampling model of group discussion were tested with 3-person teams of physicians given 2 hypothetical medical cases to diagnose. Some of the information about each case was given to all 3 team members before discussion (shared information), whereas the rest was divided among them (unshared information). As predicted, shared information was, overall, more likely to be discussed than unshared information, and it was brought into discussion earlier. In addition, it was found that team leaders repeated substantially more case information than did other members and that, over time, they repeated unshared information at a steadily increasing rate. The latter findings are interpreted as evidence of leaders' information management role in problem-solving discussions.

Adult

Influence of parboiling and physico-chemical characteristics of rice on the glycaemic index in non-insulin-dependent diabetic subjects.

OBJECTIVE: To study the influence of parboiling, amylose content and gelatinisation temperature of rice on the postprandial blood glucose and insulin responses in non-insulin-dependent diabetic (NIDDM) subjects. DESIGN AND SUBJECTS: Twelve NIDDM subjects ingested high (27%) and low amylose content five test meals of 50 g available carbohydrates as white bread, cooked polished rice with high (27%) and low amylose content (12%) with different gelatinisation temperature and as nonparboiled and parboiled. The meals were taken in random order after a 12h fast with approximately 7 days interval. RESULTS: The glycaemic indices (GI) of all rice varieties were lower than that of white bread (P <0.001). Furthermore, GI of parboiled rice with a high amylose content was lower than that of parboiled rice with a low amylose content (50 +/- 7 vs 73 +/- 7, P <0.01). No differences were 47 +/- 4, n.s.), nor between non-parboiled and parboiled rice (50 +/- 7 vs 53 +/- 7, n.s.). Insulin responses to the five test meals were not significantly different in the NIDDM subjects. CONCLUSIONS: In NIDDM subjects the investigated rices were all low glycaemic as compared to white bread,independent of parboiling and physico-chemical characteristics. The mildparboiling process used did not influence GI. The study showed that the amylose content, but not the gelatinisation temperature, may be an useful criterion in selection of low GI rices also after parboiling.

Aged

Prescribed masturbation in sex therapy: a critique.

The goal of this paper is to show from an interactional or systemic perspective how intimacy may be damaged through traditional sex therapy approaches. This is in opposition to stated claims by sex therapists, who have, since the pioneering work of Masters and Johnson, sought to improve intimacy by removing the impediment of poor sexual response. Prescribed masturbation in sex therapy is identified as particularly problematic in its potential for iatrogenic effects. These potentials are demonstrated from a relational perspective and from a functional perspective. Prescribed masturbation, intended to narrow the focus of attention from the "distraction" of a partner's response, may actually serve to further damage the openness and trust necessary for truly rewarding sexual expression. Difficulties in a relationship that preclude the trust necessary for open sexual interaction ought to be addressed before any sexual activity is prescribed. If clinicians' work circumvents the interactional component of the dysfunction, they may be guilty of colluding with clients in protecting them from intimacy. Recommended alternatives for clinicians are offered.

Behavior, Addictive

Inhibition of breast and ovarian carcinoma cell growth by 1,25-dihydroxyvitamin D3 combined with retinoic acid or dexamethasone.

This study examined the growth inhibitory effects of combining 1,25-dihydroxyvitamin D3 (calcitriol) with retinoic acid or dexamethasone against cultured breast and ovarian carcinoma cells. Retinoic acid (12.5-50 nM) increased the effectiveness of calcitriol (12.5-50 nM) against MCF-7 and NIH:OVCAR3 cells, with synergistic interactions at two of the three ratios tested. Dexamethasone augmented calcitriol effects, with synergism at 0.05 and 0.1 nM dexamethasone in MCF-7 cells and 5 nM in Caov-4 ovarian cells. This study showed favorable interactions for calcitriol-retinoic acid and calcitriol-dexamethasone combinations in breast and ovarian cancer cell lines.

Antineoplastic Agents

Cloning and characterization of a protective outer membrane lipoprotein of Actinobacillus pleuropneumoniae serotype 5.

The gene encoding an outer membrane lipoprotein (omlA) of Actinobacillus pleuropneumoniae serotype 5 was cloned, and the protein was expressed in Escherichia coli. One open reading frame of 1,104 bp was detected that encoded a protein (OmlA) with a predicted molecular mass of 40 kDa. A comparison with the omlA gene and the corresponding protein of A. pleuropneumoniae serotype 1 (G.-F. Gerlach, C. Anderson, S. Klashinsky, A. Rossi-Kampos, A.A. Potter, and P.J. Wilson, Infect. Immun. 61:565-572, 1993) revealed that the nucleic acid sequences had an overall sequence identity of 62.9% and the deduced amino acid sequences showed a sequence agreement of 57.3%. Both proteins were antigenically distinct. In a Western blot (immunoblot) analysis using a specific antiserum against A. pleuropneumoniae serotype 5 OmlA, a homologous protein was detected in the reference strains of A. pleuropneumoniae serotypes 5A, 5B, and 10. Pigs immunized with this recombinant protein were protected from death in an aerosol challenge experiment with an A. pleuropneumoniae serotype 5 isolate.

Actinobacillus Infections

Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3.

Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have been partial and of short duration, results which indicate a need for new agents and therapeutic strategies. This study was undertaken to determine the effects of carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic agent that has activity against multiple solid tumors, including ovarian carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration-dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol also inhibited RL95-2 growth in a concentration-dependent manner. Maximal inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth inhibition. The degree of interaction between carboplatin and calcitriol was assessed using isobolographic analysis and was found to be additive at all drug concentrations and ratios examined. These results suggest that carboplatin and calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that the combination of these two agents acts additively to inhibit the growth of RL95-2 cells. These agents merit further investigation for their utility against endometrial carcinomas.

Adenocarcinoma

Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25-dihydroxyvitamin D3, retinoic acid and dexamethasone.

The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western

Recidivism in a cohort of juvenile detainees: a 3 1/2-year follow-up.

We report some results from a longitudinal study of juvenile detainees. In extending previous analyses, we sought to determine whether the youth's alcohol or other drug use and their emotional/psychological problems at entry into the detention center predicted subsequent arrests for new offenses during the 36 months and 42 months following their initial interviews. Statistically significant relationships were found between the youths' demographic characteristics (age, race, gender) and cocaine use at initial interview (as measured by urinalysis), and recidivism. The policy implications of these findings are discussed.

Adolescent

Forecasting survival in the medical intensive care unit: a comparison of clinical prognoses with formal estimates.

Physicians often need to make prognostic judgments. In the present study, the accuracy was explored of survival estimates for patients in the Medical Intensive Care Unit (MICU). Estimates were made by physicians and nurses several times during each patient's stay in the MICU and were compared to those of the APACHE II scale, a widely used quantitative index for critically ill patients. ROC curve and calibration curve analyses were performed to assess the accuracy of these estimates. Results revealed that MICU personnel were fairly accurate discriminators of patients who survived vs. who died, although there was a consistent tendency to underestimate survival. In addition, there was some relationship between the level of physician training and forecasting accuracy, but only within the patient's first 24 hours in the MICU. Finally, the estimates of physicians did not differ significantly from those of the APACHE II scale. Physicians tended to be better calibrated in their predictions, while the APACHE II scale was slightly superior in terms of discrimination.

Forecasting

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol

Elevated muscle acidity and energy production during exhaustive exercise in humans.

This study examined the effect of previous intense exercise on energy production during exhaustive exercise. Subjects (n = 6) performed dynamic knee extensor exercise to exhaustion twice (Ex1 and Ex2) separated by 16 min of recovery consisting of 10 min of rest, 3.5 min of very high-intensity intermittent exercise, and a further 2.5 min of rest. This resulted in an elevated muscle lactate concentration of 13.1 mmol/kg wet wt before Ex2. Muscle lactate concentration was the same at end of Ex1 and Ex2, but the accumulation of lactate and net lactate release during Ex2 was reduced (P < 0.05) by 67 and 38%, respectively. The time to exhaustion was 3.73 and 2.98 min, respectively, and the mean rate of net lactate production for Ex2 was lower (P < 0.05) than for Ex1 (4.6 +/- 1.2 and 9.6 +/- 1.7 mmol.min-1.kg wet wt-1, respectively). Leg O2 uptake was the same for Ex1 and Ex2. Muscle pH (6.85) was lowered (P < 0.05) before Ex2, but at the end of Ex2 (6.77) it tended (P < 0.1) to be higher compared with that at the end of Ex1 (6.73). In summary, the net lactate production rate is reduced but the aerobic energy production is not significantly altered when intense exercise is repeated. Fatigue and the lowered glycolysis do not appear to be caused by the elevated acidity per se before exercise.

Acid-Base Equilibrium

Clinical criteria for the diagnosis of salivary gland hypofunction.

There is considerable difficulty in the making of initial clinical decisions as to whether a given patient has salivary gland hypofunction, and hence requires additional salivary gland evaluation. This study identified a set of four clinical measures that, together, successfully predicted the presence or absence of salivary gland hypofunction. The four measures were: dryness of lips, dryness of buccal mucosa, absence of saliva produced by gland palpation, and total DMFT; they were derived from discriminant analysis of data collected from 71 individuals with normal and low salivary flow rates. These measures are proposed as criteria for clinical decision-making, as well as for classification of patients in studies of salivary gland dysfunction syndromes. This study also identified unstimulated whole salivary flow rates of 0.12-0.16 mL/min as the critical range separating individuals with salivary gland hypofunction from those with normal gland function.

Adult

A structural model examining the relationship between physical child abuse, sexual victimization, and marijuana/hashish use in delinquent youth: a longitudinal study.

A structural model of the relationships among physical abuse and sexual victimization experiences, marijuana/hashish use (measured by self-report and urine test data) and self-reported delinquent behavior (theft crimes, index offenses, crimes against persons, drug sales and total delinquency) over time was tested in a longitudinal study of juvenile detainees. The hypothesized model was supported by the data. Theoretical, research and policy implications of the results are drawn.

Adolescent

[Pregnancy after kidney transplantation].

Renal transplantation is invariably accompanied by improvement in reproductive function. The possibility of conception in women of childbearing age emphasises the need for sensible counselling. Most authorities advise a delay of about two years post-transplantation. This appears to be good advice, because by then the patient will have recovered from the major surgical sequelae, renal function will have become stabilized with a very high probability of allograft survival at five years and immunosuppression will also be at a maintenance level. Renal function should be stable with a S-creatinine less than 130 micromoles/l. About 40% of all conceptions do not proceed beyond the first trimester. The overall complication rate in pregnancy continuing beyond the first trimester is 46%. If complications, usually uncontrolled hypertension, renal deterioration or rejection, occur before 28 weeks of gestation then successful obstetric outcome occurs in 73% compared to 92% when pregnancy is trouble-free before 28 weeks. Remote problems occur in 11% of women after delivery but where the pregnancy is complicated prior to 28 weeks remote problems occur in 24%. It is of course, difficult to know whether problems are precipitated by pregnancy or are time-dependent and would have occurred in any case.

Female