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Biomedical subjects

M Schaffer

Publications and source records attributed to M Schaffer.

At least 19 recordsLinked to original sources
PubMed2003

Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation.

In unrelated stem-cell transplantation, the value of matching at the HLA-A, -B and -DR loci between donor and recipient is well documented. The effect of HLA-C, DPB1 and DPA1 mismatches on transplantation outcome is unclear. In this study, 104 donor recipient-pairs, transplanted at Huddinge University Hospital between 1988 and 1999, were retrospectively HLA class I- and class II-typed by PCR-SSP. The samples were typed for HLA-A, -B and -C and HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPB1 and -DPA1 with allele level resolution. Isolated HLA-B allele level mismatches were associated with an increased incidence of acute graft versus host disease grades II-IV and grades III-IV. HLA-C-mismatched, but killer cell immunoglobulin-like receptor (KIR) ligand motif-matched stem-cell grafts were significantly associated with improved survival rates and relapse-free survival (RFS). In patients receiving HLA-DPA1-mismatched stem cell grafts, reduced survival and shorter RFS were seen. These patients also had an increased frequency of relapses (64%vs 26%). We conclude that genomic HLA class I- and class II-typing may improve the outcome after unrelated stem-cell transplantation. The awareness of HLA class I- and II-mismatches in a recipient-donor pair makes it possible to give appropriate pre- and post-transplantation treatment.

Epitopes↗
PubMed2003

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer--preliminary results.

BACKGROUND: The local recurrence rate of colorectal cancer has been significantly reduced due to the use of combined radiochemotherapy. Despite this improvement regarding locally advanced tumour recurrences, the treatment strategy for pre-treated patients remains difficult and unresolved. PATIENTS AND METHODS: We analysed treatment and follow-up data of 14 patients with local recurrence of rectal cancer who were treated with radiation therapy (RT), chemotherapy (CT) and regional hyperthermia (RHT) from November 1997 to December 2001. Nine of these patients had received irradiation and CT (= pre-treated patients) in the past. For this group, 30.6-39.6 Gy RT, 5-fluorouracil (5-FU) as a continuous infusion over 5 days per week (350 mg/m(2)/24 h) combined with RHT twice a week was given. The 5 remaining patients (= not pre-treated) received conformal irradiation of 45 Gy with a boost between 9 and 14.4 Gy, combined with continuous infusion of 5-FU on days 1-4, and 29-33 (500 mg/m(2)/ 24 h), and RHT twice a week. Response to therapy was evaluated by means of computed tomography (CT) or magnetic resonance imaging (MRI) and by clinical follow-up. RESULTS: Among 13 evaluated cases, the overall objective response rate was 54% (5 complete responses, 2 partial responses). At mean follow-up of 13.9 months (range 5-32 months) 7 patients were alive. CONCLUSION: The therapeutic regimen appears to be active in the treatment of local recurrences of rectal cancer. Larger-scaled studies are needed to evaluate the potency of hyperthermia in this therapeutic strategy.

Antimetabolites, Antineoplastic↗
PubMed2002

Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.

Animals↗
PubMed2002

Application of Photofrin II as a specific radiosensitising agent in patients with bladder cancer--a report of two cases.

BACKGROUND: The effect of ionizing radiation on tumour tissues can be optimised by adding radiosensitising agents to enhance tumour inactivation. Photofrin II has been approved as a photosensitising agent for the photodynamic therapy (PDT) of selected solid tumours. At present, no chemical modifier has been found to act as a selective radiosensitiser. We report here the first use of Photofrin II as a radiosensitising agent to enhance radiation therapy. PATIENTS: Two patients, one female with unresectable bladder cancer and one male with recurrent inoperable bladder cancer, were treated with radiation therapy (44.8 Gy + 14 Gy boost) of the pelvic region. 24 hours before initiation of therapy the patients were intravenously injected with 1 mg kg(-1) Photofrin II (Axcan, Canada). RESULTS: Magnetic resonance imaging of the pelvis with a standardized protocol demonstrated a reduction in tumour volume of approximately 40% in the female patient and 35% in the male patient. The female patient was operated upon after conclusion of radiotherapy, the male patient refused the operation. No severe side effects were observed. CONCLUSION: Photofrin II is a promising radiosensitising agent in the treatment of patients with advanced solid tumours.

Aged↗
PubMed2002

Radio-chemotherapy as a preoperative treatment for advanced rectal cancer. Evaluation of down-staging and morbidity.

BACKGROUND: The standard therapy for patients with clinically resectable rectal cancer is generally considered to be surgery. If the patient is diagnosed with advanced disease, postoperative radio-chemotherapy (RCT) is usually recommended. In our study we aimed to investigate and analyze the effectiveness and toxicity of preoperative pelvic radiotherapy in combination with 5-fluorouracil (5-FU) in locally advanced rectal cancer. PATIENTS AND METHODS: From June 1999 to September 2001 we evaluated 50 consecutive patients [37 male and 13 female; average age 65.1 (range 46-79.5) years] with locally advanced rectal carcinoma. 32 patients were staged as uT3, 14 as uT4, and 4 as uT2. Regarding N-staging, 22 patients were diagnosed as uN0. 2 patients had distant metastases, with liver metastases in both instances. Conformal irradiation was performed with a box technique (4-field technique) with a dose of 45 Gy (5 x 1.8 Gy per week for a total of 25 sessions). From days 1-5 and 29-33, all patients received 5-FU (500 mg/m(2 ) per day, as a continuous i.v. injection). RESULTS: Remission was observed in 28 patients (56%), with down-staging of at least one T-stage. A better success rate was achieved for patients with deep-seated tumors (64% of the patients in this group). Complete remission was observed in 4 patients (8.0%) and progression in 3 (6.0%). 15 patients had no detectable change in tumor staging (30.0%). A surgical R0 resection could be achieved in 43 patients, an R1 resection (minimal margin) in 7. Side effects and toxicity (common toxicity criteria) of RCT included grade I-II dysuria in 5 patients (10%), grade I-II diarrhea in 20 patients (40%), and severe diarrhea in 2 patients (4.0%). Grade I-II skin reaction was noticed in 22 patients (44.0%), severe skin reaction only in 1 patient. Regarding acute postoperative morbidity, abscess and fistula formation was noted in 8 patients (16.0%), with anastomosis leakage in 7 (14%). CONCLUSION: Preoperative radiotherapy appears to be a feasible therapeutic approach with moderate toxicity and the potential to induce down-staging. The data presented in this study confirm the preliminary reports on this neoadjuvant treatment.

Adult↗
PubMed2001

HLA-AB typing by polymerase-chain reaction with sequence-specific primers: more accurate, less errors, and increased resolution compared to serological typing.

Until recently, serological typing has been the primary technique used for HLA class I analysis. But because of limitations, molecular-typing techniques have replaced or supplemented the microlymphocytotoxicity test. It has been assumed that HLA class I serological typing was more accurate than serological HLA-DR typing; the latter has been shown to have 10-25% errors. But several studies have shown that HLA-AB typing was poorer than expected, and error frequencies between 5-25% were reported. This study systematically investigated the accuracy of HLA class I serological AB typing in healthy, bone-marrow registry donors, necrokidney donors, kidney-transplantation patients (on waiting lists), and haematological disorder patients. Genomic HLA class I typing, which uses polymerase-chain reaction with sequence-specific primers (PCR-SSP), gave discrepant results in 3-24% of the patients, compared to serological typings. The highest error rate (24%) was found among haematological disorder patients. Among the kidney waiting-list patients and necrokidney donors, 11% discrepancies were found. In the consecutively typed bone-marrow donors group, 3% errors were found. But among those with only one detected HLA-A specificity, 12% discrepancies were found, and among donors with only one detected HLA-B specificity, 19% errors were found. Based on these results, we recommend that patients with haematological disorders should be typed using genomic techniques. In investigations of bone-marrow registry donors and kidney patients, in which only one serological specificity is found, additional typing by genomic methods should be done.

Alleles↗
PubMed2001

Sinus node reentrant tachycardia in a neonate.

A neonate presented with paroxysmal atrial tachycardia. Transesophageal electrophysiological study demonstrated sinus node reentrant tachycardia, which was induced and terminated with programmed electrical stimulation. The tachycardia would also terminate in the atrium with adenosine. Empiric digoxin treatment successfully suppressed the tachycardia which then recurred with discontinuation of the digoxin at 6 weeks. The child was retreated with digoxin with no further recurrences for 18 months. Transesophageal electrophysiological study at 20 months showed prolonged sinus node recovery times and no inducible arrhythmias. The child has remained free of arrhythmias at 4 years.

Anti-Arrhythmia Agents↗
PubMed2001

Community interdisciplinary education to promote partnerships in family violence prevention.

Family violence is a major social and health problem in the United States. Educational approaches are needed that help professionals and communities develop more effective skills to work with families and communities. This article describes a statewide, interdisciplinary, community-based educational program for professionals and paraprofessionals and a 6-month post-evaluation. Participants reported knowledge and skill development in assessment and interventions, improved use of violence prevention data for planning and interventions, and increased community partnerships and collaborations. Recommendations address violence prevention leadership, funding, infrastructure, interdisciplinary professional education, greater community awareness, and policy development.

Cooperative Behavior↗
PubMed2001

Porphyrias associated with malignant tumors: results of treatment with ionizing irradiation.

BACKGROUND: Porphyrin metabolism disorders, known as porphyria, represent inherited or acquired diseases. The development of porphyria due to light sensibility occurs especially with exposure to wavelengths in the range of 300-700 nm. Skin reactions and neurovisceral dysfunctions are known side effects of ionizing irradiation. It can be postulated that during or after ionizing irradiation treatment of patients affected with tumor and porphyria, severe side effects might appear, in contrast to patients without porphyria. This paper describes the treatment of 2 patients affected with tumor and concomitant porphyria. PATIENTS: One female patient suffering from intermittent porphyria and breast cancer and one male patient suffering from porphyria cutanea tarda and bladder cancer were treated with ionizing irradiation (electrons and photons). No abnormalities nor any severe general or local side effects could be observed. CONCLUSION: Radiation therapy is not a 'stimulating' factor in activating porphyria symptoms.

Aged↗
PubMed2001

Photofrin II as an efficient radiosensitizing agent in an experimental tumor.

BACKGROUND AND OBJECTIVE: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. MATERIALS AND METHODS: Several series of animal experiments were performed. The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. RESULTS: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. CONCLUSION: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation.

Animals↗
PubMed2000

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II.

PURPOSE: Between 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors. METHODS AND MATERIALS: Ninety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates. RESULTS: Five-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and-with only marginal significance-radiation doses to the vulva. CONCLUSIONS: The prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the vulva should be irradiated resulting in better long-term survival.

Adult↗
PubMed2000

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser -- preliminary results.

BACKGROUND AND OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS AND METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Adult↗
PubMed2000

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI).

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Female↗
PubMed2000

Evaluating health-related quality of life: cost comparison of computerized touch-screen technology and traditional paper systems.

We estimated and compared the costs for three different methods of administering and evaluating the Short Form-36 as a routine part of clinical practice from the provider perspective. In an outpatient pain management practice, we assessed a computer touch-screen system with facsimile and scanning scoring methods. Equipment, supply, and labor costs needed to construct, maintain, and generate reports for each system were measured. The annual fixed, variable, and total costs/survey were calculated. Sensitivity analyses were performed varying the number of surveys administered/year. The facsimile method was the least costly, $9.62 and $5.88/survey, at annual questionnaire volumes of 250 and 1000, respectively. When the annual survey volume increased to 1250 (5 surveys/day), the costs of the facsimile ($5.63/survey) and computer touch-screen ($5.65/survey) methods were nearly equivalent per survey administration. At volumes of 1500 and above, the least costly method was the computer touch screen at $5.47/survey. The system implemented in a clinical practice is dependent not only on questionnaire volume but also on personnel availability, equipment access, required speed of results, and the acceptable level of data error.

Allied Health Personnel↗
PubMed1999

Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial.

BACKGROUND: Patients with atypical depression are more likely to respond to monoamine oxidase inhibitors than to tricyclic antidepressants. They are frequently offered psychotherapy in the absence of controlled tests. There are no prospective, randomized, controlled trials, to our knowledge, of psychotherapy for atypical depression or of cognitive therapy compared with a monoamine oxidase inhibitor. Since there is only 1 placebo-controlled trial of cognitive therapy, this trial fills a gap in the literature on psychotherapy for depression. METHODS: Outpatients with DSM-III-R major depressive disorder and atypical features (N = 108) were treated in a 10-week, double-blind, randomized, controlled trial comparing acute-phase cognitive therapy or clinical management plus either phenelzine sulfate or placebo. Atypical features were defined as reactive mood plus at least 2 additional symptoms: hypersomnia, hyperphagia, leaden paralysis, or lifetime sensitivity to rejection. RESULTS: With the use of an intention-to-treat strategy, the response rates (21-item Hamilton Rating Scale for Depression score, < or =9) were significantly greater after cognitive therapy (58%) and phenelzine (58%) than after pill placebo (28%). Phenelzine and cognitive therapy also reduced symptoms significantly more than placebo according to contrasts after a repeated-measures analysis of covariance and random regression with the use of the blind evaluator's final Hamilton Rating Scale for Depression score. The scores between cognitive therapy and phenelzine did not differ significantly. Supplemental analyses of other symptom severity measures confirm the finding. CONCLUSIONS: Cognitive therapy may offer an effective alternative to standard acute-phase treatment with a monoamine oxidase inhibitor for outpatients with major depressive disorder and atypical features.

Adult↗
PubMed1999

Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths.

OBJECTIVE: Although the background of laser therapy by means of low level energy and power is still only partially understood, there are nevertheless promising reports from clinical studies concerning pain treatment, the acceleration of wound healing, and the modulation of cell functions. In order to contribute to the understanding of such a phototherapeutic procedure cell experiments were performed. MATERIALS AND METHODS: The influence of light (lambda = 410, 488, 630, 635, 640, 805, and 1,064 nm and broad band white light) on the proliferation of cells was investigated on skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK1), urothelial carcinoma cells (J82), glioblastoma cells (U373MG), and mamma adenocarcinoma cells (MCF7) in a computer-controlled light treatment chamber. The cellular response was tested by way of the following methods: The rate of mitosis was determined by counting the single cells after Orcein-staining. The proliferation index measurements were based on the BrdU incorporation during the DNA synthesis. Statistics were performed using unpaired Student's t-test procedures, stating P < 0. 05 to be significant and P>0.05 not to be significant. RESULTS: Twenty-four hours after light treatment, a significant increase in the mitotic rate of J82 and HCV29 cells was determined when illuminated with lambda = 410 nm, lambda = 635 nm and lambda = 805 nm, respectively. C2 cells showed an increase only after lambda = 635 nm illumination. In all three cell lines, a maximum mitotic rate was determined after an irradiation between 4 and 8 J/cm(2), while a reduced mitotic rate was measured at 20 J/cm(2). MCF7, U373MG, and ZMK1 cells showed a slight decrease in the mitotic rate with increasing irradiation independent of the wavelength used. When an irradiation of 20 J/cm(2) was applied, all cell lines showed a slight decrease compared to the controls independent to the wavelength used. White light as well as lambda = 1,064 nm does not affect the mitotic rate in this irradiation range. No significant differences in the effects could be determined when the irradiance changed between 10 and 150 mW/cm(2) at certain irradiation values. The BrdU test did not show any significant alterations with respect to possible light induced processes compared to the controls. CONCLUSIONS: Dependent upon the irradiation parameter, light of a defined wavelength does affect the mitotic rate of both normal as well as tumor cells. It could be hypothesized that the action spectra of the cellular response indicate the participation of endogenous porphyrins and cytochromes as primary photoreceptors. Taking into account all light induced processes, the term biomodulation should preferably be used.

DNA↗
PubMed1999

Public health nursing practice guidelines: an evaluation of dissemination and use.

Public health nursing needs to build a practice on research-based knowledge. Public health guidelines are one strategy to achieve this goal. Using research-based knowledge, the Minnesota Practice Enhancement Project (MPEP) developed positive parenting and family violence prevention guidelines for public health nurses (PHNs). The purpose of this study was to evaluate the dissemination and use of the MPEP guidelines using a survey of PHNs and telephone interviews of public health nursing directors. Results indicated that respondents viewed the guidelines as important, but identified numerous barriers to integrating the guidelines into their practice. Major barriers included lack of time in their work day, complex guideline structure, and competing agency demands and priorities. Findings were consistent with Roger's Diffusion of Innovations theory, which describes factors associated with the adoption of a new idea or practice. Recommendations for effective dissemination include administrative support and structure to increase PHN intentional use of practice guidelines, a simplified guideline format, and mentorship in guideline use.

Attitude of Health Personnel↗