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Biomedical subjects

M Hanna

Publications and source records attributed to M Hanna.

At least 37 records · Page 2Linked to original sources
PubMed1998

Estimation of the partitioning characteristics of drugs: a comparison of a large and diverse drug series utilizing chromatographic and electrophoretic methodology.

1-Octanol-water log P values for a large number of standards and bioactive molecules have been correlated to the logarithm of the corresponding capacity factors determined by reversed-phase high-performance liquid chromatography, using a novel dynamically coated phase, containing phosphatidylcholine. Similarly a correlation was also obtained for log P and capacity factors determined by micellar electrokinetic capillary chromatography (MECC), involving the use of phosphatidylcholine--bile acid mixed micelles in the separation buffer. Statistical analysis of data obtained via both methods has shown that either method will give reliable log P predictions, although MECC is generally more useful for neutral and basic compounds. It is recommended that, as both methods can easily be set up in an analytical laboratory, their combined use provides rapid methodology for the confident estimation of hydrophobicity, as measured by log P for the widest diversity of chemical structures.

1-Octanol↗
PubMed1998

Synchrony in telomere length of the human fetus.

Telomere length, measured by terminal restriction fragments, was examined in tissues from human fetuses of gestational ages estimated as 15-19 weeks. The length of telomeres was similar in most fetal tissues. However, there were significant variations in telomere length among fetuses, with no apparent relationship between gestational age and telomere length. We conclude that synchrony in telomere length exists among tissues of the human fetus. This synchrony is apparently lost during extrauterine life.

Body Weights and Measures↗
PubMed1998

Rapid engraftment after allogeneic transplantation using CD34-enriched marrow cells.

Bone marrow cells expressing the surface antigen CD34 comprise approximately 1% of harvested marrow and are highly enriched for marrow progenitor cells, including the cells believed to be responsible for long-term engraftment following bone marrow transplantation (BMT). Selection of CD34-expressing cells was applied in allogeneic BMT (alloBMT) to decrease the number of T lymphocytes in the infused marrow in an attempt to prevent severe graft-versus-host disease (GVHD). We report 14 patients who underwent HLA-identical sibling-matched alloBMT with marrow-enriched for CD34 cells using the Isolex 300 SA device. Patients received total body irradiation, thiotepa, cyclophosphamide, antithymocyte globulin and methylprednisolone prior to marrow infusion. No post-transplantation immunosuppressive therapy was given except for a 5-week course of steroids. The purity of the infused marrow was 64.9+/-6.0% (mean +/- s.e.m.) CD34-positive cells and patients received a mean of 1.24+/-0.21 x 10(6) CD34 cells/kg. A mean of 9.4+/-1.7 x 10(4) CD3 T cells/kg were present in the CD34-enriched product, representing a 2.7+/-0.1 log depletion. There were no graft rejections and patients achieved a sustained absolute granulocyte count of >500 in a median of 10.5 days and a sustained platelet engraftment of >20000 untransfused in a median of 27 days. Patients were discharged a median of 21.5 days after marrow infusion. There were no instances of grade III or IV graft-versus-host disease (GVHD) and no unexpected adverse events during the transplant hospitalization. With a median follow-up of 12 months, the estimated 100 day survival is 86+/-9%. CD34 selection in alloBMT permits rapid engraftment without unanticipated toxicities.

Adolescent↗
PubMed1998

Information preferences, reading ability, and emotional changes in outpatients during the process of obtaining informed consent for autologous bone-marrow transplantation.

BACKGROUND: The complexity of autologous bone marrow transplantation (ABMT) imposes increased demands for disclosure of information to patients. This study describes the information preferences, reading ability, and emotional balance (affect) of adult patients at the time of outpatient informed consent. METHODS: Thirty patients were enrolled. The Derogatis Affects Balance Scale was used to determine each patient's emotional status before and after outpatient informed consent. The Information Styles Questionnaire was used to measure information preferences, and the Wide Range Achievement Test was used to measure reading ability. RESULTS: Every patient had at least average reading ability. Almost 90% of the patients preferred maximum amounts of detailed information. A significant change in total affectivity was seen after informed consent (p = 0.005), and the predominant pattern of change was decreases in both positive and negative affects, with a significant improvement in the positive-affects ratio. CONCLUSION: ABMT candidates tend to read well and prefer maximum amounts of information. The informed consent process is associated with significant change in the balance between positive and negative patient emotions, and the dominant pattern is neutralization of both the positive and the negative emotions. This neutralization is more pronounced for the negative emotions, suggesting that the informed consent process may make patients feel better overall.

Adolescent↗
PubMed1997

Feasibility of sequential high-dose chemotherapy and peripheral blood stem cell support for pediatric central nervous system malignancies.

BACKGROUND: The outlook for many brain tumors remains poor. Increased dose intensity has been correlated with response rate and survival in many solid tumors. PATIENTS AND METHODS: Ten children with recurrent or newly diagnosed brain tumors were treated with four sequential courses of high-dose single agent chemotherapy with peripheral blood stem cell (PBSC) support. PBSC harvesting was undertaken prior to chemotherapy and following the first course of chemotherapy (3.6 g/m2 etoposide). Each course of chemotherapy consisted of a single drug followed 48 hours later by PBSC reinfusion. Three patients were treated on Regimen A: etoposide, carboplatinum 1.95 g/m2, cyclophosphamide 5 g/m2, and thiotepa 300 mg/m2; three patients were treated on Regimen A' with carmustine 600 mg/m2 replacing cyclophosphamide; four patients received Regimen B: etoposide, carboplatinum 1.95g/m2, cyclophosphamide 7 g/m2, and thiotepa 900 mg/m2. RESULTS: No course of chemotherapy was complicated by >14 days of neutropenia. Platelet recovery was more prolonged, particularly in patients who had previously received craniospinal irradiation. Non-hematologic toxicity was severe with three toxic deaths including two patients who developed hemolytic-uremic syndrome and respiratory failure. Two of three patients with primitive neuroectodermal tumors had a partial response; no responses were observed in patients with high-grade gliomas. CONCLUSIONS: Administration of multiple courses of high-dose chemotherapy with PBSC support is feasible in this patient population and successfully mitigates hematologic toxicity. Non-hematologic toxicity becomes prohibitive as chemotherapy doses are escalated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Effects of self-care education on the health status of inner-city patients with osteoarthritis of the knee.

OBJECTIVE: To evaluate a concise program of self-care education delivered by an arthritis nurse specialist as an adjunct to primary care for inner-city patients with knee osteoarthritis (OA). METHODS: An attention-controlled clinical trial; 211 inner-city patients with knee OA were assigned arbitrarily to education (E) or attention-control (AC) conditions. Group E received an individualized 30-60-minute educational intervention that emphasized nonpharmacologic management of joint pain, preservation of function by problem-solving, and practice of principles of joint protection. Brief telephone contacts 1 week and 4 weeks later monitored and reinforced new self-care activities. Group AC viewed a 20-minute standardized public education presentation on arthritis and received followup telephone calls (only to encourage continued participation in the study). Outcomes included the Health Assessment Questionnaire (HAQ) Disability and Discomfort Scales, 10-cm visual analog scales measuring knee pain at rest and while walking, and the Quality of Well-Being (QWB) scale. Assessments were made at baseline and at 4-month intervals for 1 year. RESULTS: A total of 165 subjects (78%) completed all assessments. After control for baseline status, group E had significantly lower scores for disability and resting knee pain throughout the year of postintervention followup (P < 0.05 for both). Effects were somewhat discordant. By 12 months, functional benefits had begun to wane, while the effect on resting knee pain had grown. The overall effects of education on walking knee pain, overall joint pain (by HAQ), and general health status (by QWB) were not significant. CONCLUSION: Self-care education for inner-city patients with knee OA, delivered as an adjunct to primary care, was found to result in notable preservation of function and control of resting knee pain. The magnitude of the observed effects compares well with those of more labor-intensive and time-consuming intervention models. However, more sustained preservation of function and consistent effects on pain may require prolonged, more proactive followup, either by the patient educator or by a trained clinical assistant dedicated to the task of supporting self-care by patients with knee OA.

Aged↗
PubMed1997

Primary orthostatic tremor with prominent muscle hypertrophy.

A 33-year-old woman had a 6-year history of progressive postural instability on standing and with walking. There was progressive asymmetric lower limb muscle hypertrophy affecting thigh and calf musculature. Surface EMG recordings showed the rapid development of a synchronized motor unit discharge at a frequency of 17.5 Hz on standing, characteristic of primary orthostatic tremor. These observations suggest that primary orthostatic tremor can be associated with gait disturbance and should be considered in the differential diagnosis of unexplained muscle hypertrophy.

Adult↗
PubMed1996

Oral retinoids and pregnancy.

The oral retinoids isotretinoin and etretinate are uniquely effective in the treatment of severe cystic acne and keratinisation disorders. Because of their known teratogenicity, there are strict prescription guidelines, but exposure during pregnancy still occurs. A dedicated effort by women and their clinicians is required, involving patient selection, education and informed consent, detailed contraceptive counselling, and careful monitoring and management, including pregnancy testing before commencement of therapy.

Abnormalities, Drug-Induced↗
PubMed1996

Mutagenesis of transmembrane domain 11 of P-glycoprotein by alanine scanning.

The biochemical and genetic analyses of P-glycoprotein (P-gp) have indicated that the membrane-associated regions of P-gp play an important role in drug recognition and drug transport. Predicted transmembrane domain 11 (TM11) maps near a major drug binding site revealed by photoaffinity labeling, and mutations in this domain alter the substrate specificity of P-gp. To investigate further the role of TM11 in P-gp function in general, and substrate specificity in particular, each of the 21 residues of TM11 of the P-gp isoform encoded by the mouse mdr3 gene was independently mutated to alanine, or to glycine in the case of endogenous alanines. After transfection and overexpression in Chinese hamster ovary cells, pools of stable transfectants were analyzed for qualitative or quantitative deviations from the profile of resistance to vinblastine, adriamycin, colchicine, and actinomycin D displayed by the wild-type protein. While mutations at eight of the positions had no effect on P-gp function, 13 mutants showed a 2-10-fold reduction of activity against one of the four drugs tested. Although the phenotype of individual mutants was varied, replacements at most mutation-sensitive positions seemed to affect the drug resistance profiles rather than the overall activity of the mutant P-gp. When TM11 was projected in a alpha-helical configuration, the distribution of deleterious and neutral mutations was not random but segregated with a more hydrophobic (mutation-insensitive) face and a more hydrophilic (mutation-sensitive) face of a putative amphipathic helix. The alternate clustering pattern of deleterious vs neutral mutations in TM11 together with the altered drug resistance profile of deleterious mutants suggest that the more hydrophilic face of the TM11 helix may play an important structural or functional role in drug recognition and transport by P-gp. Finally, the conservation of the two residues most sensitive to mutations (Y949 and Y953) in TM11, and in the homologous TM5, of all mammalian P-gps and also in other ABC transporters, suggests that these residues and domains may play an important role in structural as well as mechanistic aspects common to this family of proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study.

PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

Abdomen↗
PubMed1996

An evaluation of the copper-bromide laser for treating telangiectasia.

BACKGROUND: Copper bromide lasers, producing pulsed yellow and green light, have been developed for treating cutaneous lesions. OBJECTIVE: A clinical trial was conducted to evaluate the role of this laser, using its yellow wavelength, to treat benign vascular ectasia and establish some clinical guidelines for therapy. METHODS: Twenty-three informed consenting adults with facial telangiectasia, spider angiomas, or vascular nevi on the head, neck, or upper chest were treated with the laser. Assessment of results was performed by: blinded clinical evaluation, blinded comparison of "before" and "after" photographs, and patients' own reports of satisfaction levels. RESULTS: Good to excellent results were obtained in most patients, except for a few suffering minor skin atrophy where very large vessels were treated. CONCLUSIONS: The copper bromide laser was an effective tool in the treatment of certain cutaneous vascular lesions.

Adult↗
PubMed1996

Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation.

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.

Adolescent↗
PubMed1995

Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg tablet.

Nineteen of 25 patients (14 female) with advanced malignant disease completed a randomized controlled trial of a new high-dose (200 mg) tablet formulation of controlled-release morphine. Compared with the currently available 100-mg tablets there were no differences in pain severity or adverse effects with the new formulation. In four patients, full 12-hr plasma morphine concentration profiles at steady state were obtained and showed no significant differences between the same dose provided as 100-mg and 200-mg tablets in Cmax, tmax, or other pharmacokinetic indices.

Adolescent↗
PubMed1995

Terminations of pregnancy for exposure to oral retinoids in South Australia, 1985-1993.

The oral retinoids, isotretinoin and etretinate, are highly teratogenic drugs which have been available in Australia since 1985 because of their unique effectiveness in severe cystic acne, psoriasis and other keratinization disorders. Only dermatologists can prescribe them, but in spite of strict guidelines by the manufacturers and the College of Dermatologists, exposed pregnancies have occurred. We attempted to determine the circumstances of exposure to these drugs for the 18 pregnancies terminated in South Australia in 1985-1993, using questionnaires to medical practitioners who notified the terminations under legislation. The main reason for their occurrence was the lack of compliance with the use of effective contraception by the women. In South Australia, some prescriptions of oral retinoids by unauthorized doctors have been dispensed during this period. Using statistics on prescriptions dispensed, an estimate was made of 1 termination of pregnancy for 319 courses of treatment for women with isotretinoin. Extension of guidelines for prescription and more detailed counselling in relation to the use of contraception are recommended. It is also suggested that doctors intending to recommend terminations obtain consent to discuss exposure with the dermatologists concerned, who may not be aware of the exposed pregnancy.

Abortion, Induced↗