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Biomedical subjects

C Christensen

Publications and source records attributed to C Christensen.

At least 19 recordsLinked to original sources

Phototoxic reaction and porphyrin fluorescence in skin after topical application of methyl aminolaevulinate.

BACKGROUND: Photodynamic therapy using topical methyl aminolaevulinate (MAL) is a new treatment modality for skin disorders. MAL is metabolized into endogenous porphyrins, which act as photosensitizers when illuminated. OBJECTIVES: To evaluate the severity and duration of skin photosensitivity after MAL application, and to investigate its relation to the presence of endogenous porphyrins. METHODS: Placebo and 160 mg g(-1) MAL creams were randomly assigned to contralateral sites located at the forearms and fingertips of 16 healthy volunteers and were applied for 3 h. The porphyrin content in the skin was monitored by in situ fluorescence measurements following cream removal. Phototoxic reaction was evaluated after exposure to a high dose of red light. RESULTS: The porphyrin fluorescence in forearm skin peaked about 1 h after the cream removal, was halved after 8 h, and was reduced by > 90% within 24 h. Most forearm sites were photosensitive at 1 and 8 h following cream removal. Six subjects were still sensitive at 24 h, and at this time point the phototoxicity was coincidental with residual porphyrin fluorescence. In general, all reactions were mild or moderate, and included pain, erythema, oedema and transient hyperpigmentation. No photosensitivity or porphyrin fluorescence was detected at 48 h. At the fingertips photosensitivity was absent except for sporadic cases of mild pain. CONCLUSIONS: Topical MAL application and exposure to red light induced mild and moderate phototoxicity. The photosensitivity ceased within 24-48 h after cream removal, and its duration was associated with the degradation of porphyrins.

Administration, Topical↗

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.

Adolescent↗

Uncertainty in predictions of the climate response to rising levels of greenhouse gases.

The range of possibilities for future climate evolution needs to be taken into account when planning climate change mitigation and adaptation strategies. This requires ensembles of multi-decadal simulations to assess both chaotic climate variability and model response uncertainty. Statistical estimates of model response uncertainty, based on observations of recent climate change, admit climate sensitivities--defined as the equilibrium response of global mean temperature to doubling levels of atmospheric carbon dioxide--substantially greater than 5 K. But such strong responses are not used in ranges for future climate change because they have not been seen in general circulation models. Here we present results from the 'climateprediction.net' experiment, the first multi-thousand-member grand ensemble of simulations using a general circulation model and thereby explicitly resolving regional details. We find model versions as realistic as other state-of-the-art climate models but with climate sensitivities ranging from less than 2 K to more than 11 K. Models with such extreme sensitivities are critical for the study of the full range of possible responses of the climate system to rising greenhouse gas levels, and for assessing the risks associated with specific targets for stabilizing these levels.

Journal Article↗

The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor.

The involvement of Mts1(S100A4), a small Ca(2+)-binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identified. Here we demonstrated that Mts1(S100A4) had significant stimulatory effect on the angiogenesis. We detected high incidence of hemangiomas--benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis.

Angiogenesis Inducing Agents↗

Hepatitis A vaccine administration: comparison between jet-injector and needle injection.

INTRODUCTION: Type A hepatitis virus (HAV) is a serious health problem throughout the world and can be spread via fecal-oral contact. Both immune globulin and an HAV vaccine provide protection, but the vaccine gives complete protection. Efficacy of methods of vaccination in relation to the formation of anti-HAV antibodies is unclear; thus, this study seeks to determine if significant differences exist between the syringe as compared to the jet injection technique. The purpose of this study was to compare in a randomized trial Biojet jet-injection system to a needle-syringe method. To determine if a significant difference between these two methods in seroconversion rates or geometric mean titers of anti HAV antibody occurs at day 15, 30, and 210 days after vaccination. METHOD: Anti-HAV IgG(-) adult hospital employees were randomized to receive 1440 EL.U of hepatitis a vaccine (HAVRIX(R)) in 2 doses by either needle or jet-injector (Biojector(R)) system at month 0 and 6. HAV seroconversion titer results were measured by the Boehringer-Mannheim method. RESULTS/DISCUSSION: A higher proportion of persons who received HAV vaccine via the Biojector(R) seroconverted with anti-HAV level >/=20 mIU at day 15, 30, and month 7 when compared with a needle injection.Side-effect profiles reported by participants in both methods were below those identified in current published and insert information, but the Biojector(R) had greater local reactivity in all categories when compared to the needle method.

Adult↗

Effects of prognosis, perceived benefit, and decision style on decision making and critical care on decision making in critical care.

OBJECTIVE: To assess the effects of prognostic estimates, perceived benefit of treatment, and practice style on decision-making in critical care. DESIGN: Randomized assignment of subjects to either of two versions of a questionnaire designed to elicit treatment decisions for six intensive care unit cases based on actual patients. One version offered optimistic survival forecasts; the other, pessimistic forecasts. SUBJECTS: A random sample of 120 clinicians obtained from the Canadian Critical Care Society was contacted by mail. One version of the questionnaire was randomly assigned and mailed to each. Thirty-four replies, 17 for each version (response rate, 28%), were received and analyzed. MEASUREMENTS AND MAIN RESULTS: A list of treatment/management options was developed for each case, in three categories: recommended, questionable, and unacceptable. Subjects were also able to list new options that they would order that were not on the list. The dependent variables were the number of actions ordered in each category and the total for each case. Perceived benefit was measured by comparing subjective estimates of the probability of survival with the optimistic/pessimistic forecast given in the case. Practice style was assessed by correlating the total number of actions ordered across all possible pairs of cases. There were no significant differences between the two questionnaires on actions ordered either by category or by amount per category. Perceived benefit did not appear to be an important factor in decision-making. However, statistically significant correlations provide evidence for practice style in intensive care unit decision-making on an interventionist/noninterventionist dimension. CONCLUSIONS: There is no evidence that erroneous or biased prognostic estimates affect intensive care unit treatment choices. Neither the principle of maximizing expected utility nor the Rule of Rescue appear to affect these decisions systematically, but practice style does.

Canada↗

Radiation therapy for endometrial cancer in patients treated for postoperative recurrence.

PURPOSE: To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence. MATERIALS AND METHODS: Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months). RESULTS: The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control. CONCLUSION: Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to be developed for this high-risk group of patients.

Adult↗

Diagnosing groups: the pooling, management, and impact of shared and unshared case information in team-based medical decision making.

The impact of group discussion on the decision-making effectiveness of medical teams was examined. Three-person teams of physicians diagnosed 2 hypothetical medical cases. Some of the information about each case was given to all team members prior to discussion (shared information), whereas the rest was divided among them (unshared information). Compared with unshared information, shared information was more likely to be pooled during discussion and was pooled earlier. In addition, team leaders were consistently more likely than other members to ask questions and to repeat shared information and, over time, also became more likely than others to repeat unshared information. Finally, pooling unshared (but not shared) information improved the overall accuracy of the team diagnoses, whereas repeating both shared and unshared information affected bias (but not accuracy) in the diagnoses.

Adult↗

Postoperative radiation for cervical cancer with pathologic risk factors.

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.

Adult↗

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↗

Aphthous vaginal ulceration in two women with acquired immunodeficiency syndrome.

Two women with advanced human immunodeficiency virus infection are described who were seen with painful aphthous vaginal ulceration and CD4+ lymphocyte counts < 50 cells/mm3. A chronic rectovaginal fistula developed in one patient. In spite of extensive investigation no underlying cause of the ulceration was discovered. Clinical therapeutic response suggests that corticosteroid therapy may be of value in healing or stabilizing the destructive process. Clinicians should be aware of this complication in human immunodeficiency virus-infected women with severe vaginal pain and unexplained discharge.

Acquired Immunodeficiency Syndrome↗

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↗