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Biomedical subjects

S Abdel-Rahman

Publications and source records attributed to S Abdel-Rahman.

At least 19 recordsLinked to original sources

[MRI-assisted thermometry for regional hyperthermia and interstitial laser thermotherapy].

PURPOSE: To demonstrate the potential of quantitative MRI-assisted thermometry for the treatment of tumor patients with regional hyperthermia (RHT) and interstitial laser thermotherapy (ILTT). METHODS: Two patients and seven tissue samples were investigated using the T1-relaxation time and the chemical shift of the proton resonance frequency (PRF) as temperature sensitive MRI-parameters at 0.2 and 1.5 T. Thermotherapy was applied using either a dedicated MRI-hyperthermia hybrid system or a temperature controlled laser with 830 nm. RESULTS: Both patients were treated successfully showing clinical benefit. T1 and PRF are depending on the applied thermotherapy method and on the MR-system suitable for MRI-assisted thermometry. The clinical application based on phantom results is not necessarily adequate. CONCLUSION: Clinical application and phantom experiments of RHT and ILTT show the potential of MRI-assisted thermometry for further improvement of both minimal invasive thermotherapy methods. Further investigations concerning optimization of the MRI-techniques, the influence of perfusion or the determination of threshold values are necessary.

Adult↗

[Principles, technology and indication of hyperthermia and part body hyperthermia].

Clinical hyperthermia with controlled alteration of temperature (40 to 44 degrees C) in the target area is used in interdisciplinary treatment concepts for tumor treatment in combination with radiation and/or radiotherapy. Besides the direct cytotoxic power of hyperthermia there is an immunomodulatory effect and a radiation and chemotherapy sensitizing effect in the heated tissue. Clinical hyperthermia is an invasive or non-invasive supply of energy to the body of the patient, which leads to an artificial heating of the tumor and the surrounded tissue. The clinical hyperthermic procedures should take into account the oncologic disease and its pattern of organ involvement. There are three different types of hyperthermia: local hyperthermia (LHT), regional hyperthermia (RHT) and part body hyperthermia (PBH). PBH is used to heat regions of the body in case of metastatic disease, e. g. to the abdomen. I and phase II trials could show that the effects of radiation and chemotherapy can be altered by the simultaneous addition of hyperthermia. Data of trials involving skin metastasis in malignant melanoma, local relapse in breast cancer, tumors of the head and neck with regional lymph node metastasis, as well as trials in colorectal tumors, bladder cancer, pancreatic cancer, cervical cancer and sarcoma are presented. The results shows, that response to treatment can be improved by hyperthermia.

Combined Modality Therapy↗

Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen alone and in combination with regional hyperthermia is active in chemo-pre-treated advanced soft tissue sarcoma of adults.

PURPOSE: To evaluate the efficacy and safety of the combination of ICE (ifosfamide 1.5 g m(-2), carboplatin 100 mg m(-2) and etoposide 150 mg m(-2), days 1-4, q 28 days, G-CSF 5 microg kg(-1) starting from day 6) alone and in combination with regional hyperthermia (RHT) in soft tissue sarcoma (STS) refractory to previous standard doxorubicin-ifosfamide-based chemotherapy. PATIENTS AND METHODS: Twenty patients with advanced STS of different histological sub-types were treated with the ICE regimen with 13 patients receiving additional RHT. A median of four courses of ICE were administered with RHT on days 1 and 3 (60 min, T(max) 42 degrees C). RESULTS: The objective response rate was 20%, with four partial responses (all treated with hyperthermia). In addition, two patients showed mixed responses and five patients stable disease. After a median follow-up time of 15 months, median time to progression was 6 months. Progression free rate estimates were 60% and 45% at 3 and 6 months, respectively. Median overall survival for all patients was 14.6 months. CONCLUSION: These results suggest that ICE alone or combined with RHT shows activity as second-line therapy in doxorubicin-ifosfamide-refractory STS.

Adolescent↗

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↗

Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults: long-term results of a phase II study.

In this phase II study, activity and safety of neoadjuvant regional hyperthermia (RHT) combined with chemotherapy was investigated in 59 patients with primary advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT followed by surgical resection and adjuvant treatment. The overall objective response (OR) rate was 17%, with one complete (2%) and eight partial (15%) responses. In addition, 13 minor responses (25%) were seen. At time of surgery, complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable histological response (FHR)) in 12 patients. At the completion of protocol treatment, 36 patients were rendered disease-free which was significantly associated with the initial radiographic and/or pathological tumour response (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow-up of 82 months, local treatment failure occurred in 33 patients, median overall survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence interval (CI): 36-61%). OS which did not differ for extremity versus non-extremity STS (P=0.21) was better for patients responding to EIA combined with RHT (P<0.01).

Adult↗

Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia.

The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44-73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.

Adult↗

[MRI-controlled regional hyperthermia].

PURPOSE: Regional hyperthermia in combination with chemotherapy or/and radiotherapy is a promising treatment concept for locally advanced, deep-seated tumors. The purpose of the project is the optimization of the therapy using non-invasive, three-dimensional imaging of tissue changes or of the temperature distribution during regional hyperthermia. METHODS: MRI offers methods suitable in principle for tissue characterization and MR thermometry. A new MRI-hyperthermia hybrid system has been developed based on an innovative hyperthermia applicator and an open MRI system. RESULTS: After successful testing of the new MRI-hyperthermia hybrid system simultaneous MRI and regional hyperthermia in patients could be accomplished for the first time. At present the T1 relaxation time seems to be a promising parameter for MR thermometry. CONCLUSION: The first clinical application of the MRI-hyperthermia hybrid system can be regarded as an important step towards the development of regional hyperthermia. This new hybrid system and the MR thermometry methods have to be investigated prospectively in clinical studies.

Equipment Design↗

Biochemical characterization and localization of Fasciola hepatica 26-28 kDa diagnostic coproantigen.

We have previously reported the usefulness of a 26-28 kDa coproantigen of Fasciola hepatica for diagnosis of infection. In this study, the 26-28 kDa coproantigen was biochemically characterized with the aid of monoclonal antibodies (MoAb) in an effort to better understand the biology of the antigen. Differential staining of chromatographically-purified 26-28 kDa coproantigen on SDS-PAGE, under reducing and non-reducing conditions, indicated that the coproantigen was a monomeric, highly glycosylated glycoprotein. Alkaline treatment of the purified coproantigen resulted in an 8 kDa protein core which still contained the epitope recognized by the MoAb. No protease activity was associated with the 26-28 kDa coproantigen. The coproantigen could be cleaved by trypsin without altering the reactive epitope recognized by the MoAb, but was resistant to pepsin digestion. Further, the coproantigen was stable under several different storage conditions. Indirect immunofluorescence on tissue sections of adult flukes indicated that the coproantigen was present in gut cells and tegument. Taken together these results confirm the stability of the 26-28 kDa coproantigen and its usefulness in diagnostic tests for F. hepatica infections.

Animals↗

Rifapentine pharmacokinetics in adolescents.

OBJECTIVE: Determination of rifapentine pharmacokinetics in healthy adolescent children. DESIGN: Prospective Phase II clinical trial. SETTING: Clinical research center within a university children's hospital. PATIENTS: Twelve subjects ranging in age from 12 to 15 years, male and female. INTERVENTIONS: A single oral dose of rifapentine was administered to healthy adolescent volunteers, 450 mg if <45 kg or 600 mg if > or =45 kg. Blood was collected at serial intervals (0, 2, 3, 4, 5, 6, 8, 12, 18, 24, 48 and 72 h postdose). Subjects were observed for adverse effects during the period of study. MEASUREMENTS: High pressure liquid chromatography was used to measure the plasma concentration of rifapentine and 25-desacetyl rifapentine in each blood sample. For each subject a plot of mean plasma concentration vs. time data for rifapentine and its metabolite (i.e. 25-desacetyl rifapentine) were created. Subsequently model-independent methods were used to determine the pharmacokinetic profiles for each subject. RESULTS: All subjects tolerated rifapentine without adverse effects. The 2-h postdose plasma concentrations of rifapentine (6.59 to 9.05 microg/ml) and 25-desacetyl rifapentine (0.57 to 2.64 microg/ml) far exceeded the MIC of Mycobacterium tuberculosis to rifapentine (approximately 0.12 microg/ml). The combination of a high Cmax (rifapentine, 9.95 to 18.63 microg/ml; 25-desacetyl rifapentine, 3.73 to 7.46 microg/ml) and lengthy terminal elimination phase t1/2 (rifapentine, 10 to 23 h; 25-desacetyl rifapentine, 14 to 35 h) resulted in potentially effective plasma concentrations of both compounds that persisted for at least 48 h in most subjects. CONCLUSIONS: A well-tolerated oral rifapentine dose produced rapid and sustained plasma drug concentrations in adolescents that should effectively treat infections caused by M. tuberculosis. Rifapentine pharmacokinetics appears to be similar in adolescent and adult populations.

Adolescent↗

Studies on prenatal infections in children with unknown cause of mental retardation and examination of their mothers.

Specific IgG antibodies against Toxoplasma, rubella, cytomegalovirus and herpes simplex (TORCH agents) were investigated in 32 infants and children with unexplained mental retardation (MR) and their mothers. 16 mentally normal infants and children of the same age group and their mothers were chosen as controls. Specific Toxoplasma IgG antibodies were 43.75% for MR cases and 37.5% for their mothers. Six (18.75%) mothers gave history of eating raw meat and canned food, while 8 (25%) had pet cats. 56.25% of the MR cases, and 81.25% of their mothers were positive to specific rubella IgG antibodies. 75% of MR cases and 81.25% of their mothers were positive for CMV specific IgG antibodies. Also, 18.75% of the MR cases and 25% of their mothers showed positivity to herpes simplex specific IgG antibodies. 93.75% showed positivity to one or more of the mentioned pathogenic agents.

Adult↗

Stability of pentoxifylline in an extemporaneously prepared oral suspension.

The stability of pentoxifylline in an extemporaneously prepared suspension was studied. Twelve 400-mg pentoxifylline tablets were crushed and mixed with water to prepare a 20-mg/mL suspension. The suspension was transferred to 10 amber glass and 10 amber plastic prescription bottles. Five glass and five plastic bottles were stored at 25 degrees C, and the rest were stored at 4 degrees C. Samples were collected before storage and on days 7, 14, 21, 28, 42, 56, 70, and 91 and analyzed in duplicate by stability-indicating reverse-phase high-performance liquid chromatography. Pentoxifylline was stable in the suspension under all storage conditions for the duration of the study. The color, odor, and pH of the suspension did not change appreciably. Some settling of the suspension was noted in all bottles beginning on day 21, but shaking resuspended the settled material. Pentoxifylline 20 mg/mL was stable in an extemporaneously prepared suspension for at least 91 days at 25 or 4 degrees C.

Chromatography, High Pressure Liquid↗

Inhibition of prophage induction by synthetic pentapeptide.

Six peptide chains different in length and number of sequences were synthesized by the continuous-flow solid-phase method. Their effects on prophage induction were tested. It was found that pentapeptide 1 H-Val-Val-Asn-Asp-Leu-OH, at a concentration of 25 micrograms/mL inhibited the spontaneous induction of prophage Lambda in E. coli strain W 3110(lambda) and phi RLZLS in R. leguminosarum (lysogenic local isolate) by 99.5% and 65.7%, respectively. Moreover, this concentration was also able to inhibit the replication of the developed phages in the indicator strains. It was suggested that this peptide may block the attachment site of the induced phages or inhibit Rec A Protease.

Bacteriophage lambda↗

Characterization of heptapeptide toxins extracted from Microcystis aeruginosa (Egyptian isolate). Comparison with some synthesized analogs.

Four toxic peptides from local fresh water cyanobacterium Microcystis aeruginosa were purified and identified by high performance liquid chromatography (HPLC) and ion spray mass spectroscopic studies as: RR; YR; LR and LA with molecular weights of 1006.8, 1073, 984.8 and 910.6 respectively. Amino acid analysis indicated the presence of equimolar amounts of aspartic acid, glutamic acid, arginine, leucine and tyrosine, in addition to both alanine and dehydroalanine. Mouse assay toxicity indicated that the first two peptides, at the peak area of RR, YR, were highly toxic with LD50 20, 18.2 micrograms/kg body weight; however, the latter two, at the peak areas LR and LA, have a lesser toxicity with LD50 36 and 40 micrograms/kg body weight respectively. Three linear peptide analogs to those naturally found devoid of Adda were synthesized using the continuous flow technique. HPLC pure synthesized analog products were tested for toxicity using male mice (i.p. injection). None of them induced toxic activity.

Amino Acid Sequence↗

Preoperative systemic etoposide/ifosfamide/doxorubicin chemotherapy combined with regional hyperthermia in high-risk sarcoma: a pilot study.

From November 1990 to September 1991, 23 adults with high-risk, nonmetastatic sarcomas (20 soft-tissue sarcomas and 3 chondrosarcomas) were entered in a pilot protocol (RHT-91) involving regional hyperthermia combined with systemic chemotherapy followed by surgery. Of these patients, 12 had undergone previous surgery and/or radiation, 5 had received previous multidrug chemotherapy, and 6 were previously untreated. A tumor size of > 8 cm and/or an extracompartmental tumor location (11 patients) or local recurrence (12 patients) were defined as high-risk factors in addition to tumor grading (21 patients had grade 2 or 3 sarcomas). Regional hyperthermia was produced by an electromagnetic deep-regional-heating device. For systemic chemotherapy, all patients received etoposide/ifosfamide/doxorubicin (EIA) and mesna, with regional hyperthermia being given only on days 1 and 4 in repeated EIA/regional hyperthermia cycles every 3 weeks. Tumor temperatures (range, 40 degrees-44 degrees C) were measured by invasive thermometry in all patients during each regional hyperthermia treatment. A total of 181 regional hyperthermia treatments were applied within the pelvic region (11 patients) or extremities (12 patients) bearing relatively large tumors (mean volume, 848 cm3). By the cutoff date for this analysis (October 15, 1991), 13 patients had undergone surgery after receiving 2-6 (mean, 3.8) cycles of EIA chemotherapy combined with regional hyperthermia; all tumors except one were resected without disfiguration. In 22 evaluable patients (minimum, 2 EIA plus regional hyperthermia cycles), the clinical response rate was 27%, with 6 patients showing partial responses (PRs). In addition, a pathologic response to preoperative thermochemotherapy was evaluable in 13 patients, with 4 responders (31%) having > 50% histologic necrosis. In all, 3 of the responders (1 PR and 2 patients with > 50% histologic necrosis) relapsed within 3 months of surgical resection. The other 7 responding patients (5 PRs and 2 patients with > 50% histologic necrosis) showed stable disease with local tumor control. The study (RHT-91) is continuing as a multicenter phase II trial (opened on November 19, 1991) in patients with high-risk soft-tissue sarcomas to test the potential of preoperative thermochemotherapy in regard to local control and survival.

Adolescent↗

Intrinsic innervation and vasculature of pre- and post-natal human thymus.

Human thyro-thymic venous connections were more numerous in pre-natal life. The thymus was vascular since the 10th week. At 11 weeks, nerves invaded the capsule and a few trabeculae. At 16 weeks, nerve bundles accompanied arteries and veins. Their branches ran close to intralobular arterioles and venules. Parenchymal nerves appeared in the cortex and medulla. Radial cortical capillaries drained into capsular venules at 20 weeks. From 28 weeks pre-natally to 3 years post-natally, nerves in the medulla ended in knobs or fine tapers. Some encircled or relayed on Hassall's corpuscles. Others were traceable to blood vessel walls. The pattern of innervation and vascularization was not altered up to 9 years. The vasculature began to be irregular at 11--13 years. Parenchymal and perivascular nerves existed up to 15 years. At 25 years, nerves were detected in the capsule and proximal parts of the trabeculae.

Adolescent↗