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Biomedical subjects

T E Williams

Publications and source records attributed to T E Williams.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization and distribution of basic fibroblast growth factor-containing cells in the rat hippocampus.

Basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor family, is present in relatively high levels in the brain where it may play an important role in the maintenance, repair, and reorganization of the tissue. Although bFGF is associated mainly with astrocytes throughout most of the central nervous system (CNS), a narrow but prominent band of pyramidal neurons, which coincides with the CA2 subregion of Ammon's horn in the hippocampus, stains intensely for bFGF. In order to gain an understanding of which cells express bFGF and whether or not BFGF is a good marker for CA2 neurons, we have used a mouse monoclonal antibody directed against recombinant human bFGF to characterize the distribution and localization of bFGF expression in the hippocampus. We find that about one-quarter of the neurons in CA2 are bFGF positive, and they appear smaller and have more irregular-shaped nuclei than their unstained counterparts. In addition, all glial fibrilary acidic protein (GFAP)-positive astrocytes in the hippocampus stain for bFGF, and the distribution of these astrocytes is heterogeneous in the hippocampus. Finally, in both astrocytes and CA2 pyramidal neurons, bFGF immunoreactivity is localized primarily in the nucleus and to a lesser extent in the cytoplasm and processes of stained cells.

Animals↗
PubMed1996

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.

Bone Marrow Transplantation↗
PubMed1996

Visual perceptions of head-fixed and trunk-fixed anterior/posterior axes.

The purpose of the present experiment was to determine the preferred visual "straight ahead" or anterior/posterior (a/p) axis at the perceptual level. The ability of 12 neurologically normal, young adult subjects to position a rod parallel to the head and trunk a/p axes while viewing eccentrically located visual targets were studied under six conditions: 1. fixed-subjects stood erect with the head aligned to the trunk and viewed a central target while visually aligning a hand-held rod to the head and trunk a/p axis. 2. eyes-subjects moved only their eyes to view eccentric targets and aligned the rod to the head and trunk a/p axis. 3. head-trunk-subjects viewed the eccentric targets by rotating the head about a vertical axis and aligned the rod to the trunk a/p axis. 4. head-head-subjects viewed the targets as in 3 and positioned the rod parallel to the head a/p axis. 5. trunk-head-subjects viewed the targets by rotating the trunk and head as a unit about the vertical axis and aligned the rod parallel to the head a/p axis (note that the head and trunk a/p axes were misaligned by the experimenter prior to target viewing). 6. trunk-trunk-subjects viewed targets as in 5 and positioned the rod parallel to the trunk a/p axis. Subjects performed 25-35 consecutive trials within each condition. Perceptual errors were similar for aligning the rod to the trunk and head a/p axes; however, moving the trunk produced much larger constant and variable perceptual errors than moving the head. In a second experiment, four subjects controlled the position of a lighted rod held by a robot arm in complete darkness. They were instructed to align the rod to either the head or trunk a/p axis under conditions similar to the fixed, head-trunk, and head-head tasks described above. Perceptual errors were much larger when aligning the rod to the head a/p axis than to trunk a/p axis when the head was moved. This shows that the trunk a/p axis is clearly preferred at the perceptual level when visual background cues are not present. These data strongly suggest that the visual coordinate system uses a trunk-fixed a/p axis to define the subjective straight-ahead direction and right/left position of a target. Implications of these findings for sensorimotor transformations in control of upper limb movements to visual targets are discussed.

Adult↗
PubMed1996

Photodynamic therapy for esophageal malignancy: a prospective twelve-year study.

BACKGROUND: We wanted to determine factors affecting survival rates of benefits to, and complications in patients with esophageal cancer treated with photodynamic therapy. METHODS: From 1982 to January 1994, we used photodynamic therapy to treat 77 patients with esophageal carcinoma and evaluated survival to July 1994. All patients had failed, refused, or were ineligible for surgical intervention, ionizing radiation therapy, or chemotherapy. RESULTS: The only significant variable affecting survival was clinical stage. Median survival after photodynamic therapy was as follows: all patients, 6.3 months (mean survival, 9.2 months); stage I, not reached; stage II, 12 months; stage III, 6.2 months; and stage IV, 3.5 months. For stages III and IV, a Karnofsky performance status of 70 or higher had a significant effect. For stage III, the median survival was 6.3 months when the Karnofsky performance status was equal to or greater than 70 and 3.5 months when it was less than 70. For stage IV, the median survival was 5.5 months when the Karnofsky performance status was equal to or greater than 70 and 2.5 months when it was lower than 70. Seven stage I patients with no treatment prior to photodynamic therapy had an estimated 5-year survival rate of 62%. Three patients with stage I invasive adenocarcinoma and Barrett's mucosa diagnosed when they underwent endoscopy for dysphagia were alive with no evidence of disease 17, 44, and 59 months after photodynamic therapy. CONCLUSIONS: Photodynamic therapy for esophageal carcinoma caused minimal complications and no procedure-related deaths. Photodynamic therapy can be considered an alternative treatment for patients with Barrett's esophagus with severe dysplasia or patients with stage I carcinoma who are under consideration for operation but are high surgical risks. The length of palliation for patients having "noncurative" treatment was equal to or better than that reported historically for most other treatment regimens.

Adenocarcinoma↗
PubMed1996

Cerebellar dysplasia and unilateral cataract in Marinesco-Sjögren syndrome.

The classic features of Marinesco-Sjögren syndrome include bilateral cataracts, cerebellar ataxia, and mental deficiency with an autosomal recessive inheritance pattern. Weakness and a variety of other characteristics are present inconsistently. A limited number of neuroimaging studies have indicated that cerebellar hypoplasia is the most common finding. We report a patient with near normal intelligence, unilateral cataract, and the previously unreported magnetic resonance imaging findings of cerebellar dysplasia, arachnoid cyst, and absent septum pellucidum. A review of the literature suggests significant heterogeneity in the Marinesco-Sjögren syndrome.

Cataract↗
PubMed1994

Can we afford to do cardiac operations in 1996? A risk-reward curve for cardiac surgery.

Parsonnet risk estimates and postoperative lengths of stay were studied for two cohorts of cardiac surgical patients. The first cohort consisted of 287 patients and was taken from 1984, the first full year of this cardiac surgical program. The second cohort consisted of all 1,167 patients operated on in the calendar years 1989 to 1991. We found that the mean risk for the patients had nearly doubled in this interval and that the risk distribution changed significantly from one skewed toward good-risk patients to a nearly uniform distribution through all risk categories. A high correlation was identified (0.9761) between the postoperative length of stay and the mean risk estimates for the 1989 to 1991 cohort of patients. This permits a regression equation to be calculated showing that the length of stay could be estimated at 7.06 days + 0.21 times the mean risk for a patient or cohort of patients. This relationship is then used to develop a relationship between the net income for a given case or cohort of patients and the length of stay or risk. These data suggest that, in most hospitals, hospital fixed costs are a major determinant, even more so than daily charges, of the relationship between the hospital's finances and the mean risks of patients undertaken in the cardiac surgical program. The consequences of this are discussed.

Algorithms↗
PubMed1994

Ocular pharmacokinetics of orally administered azithromycin in rabbits.

Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye. At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC. Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5 micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body ( > 15 micrograms). Measurable tissue levels persisted for at least 120 hours. Trough levels increased proportionately during drug multiple dose administration. Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g. Aqueous humor and serum levels were equivalent. Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular cataract extraction did not significantly affect drug uptake.

Administration, Oral↗
PubMed1993

Phase I trial of trimetrexate in pediatric solid tumors: a Pediatric Oncology Group study.

Trimetrexate (TMTX), a lipophilic antifol, was evaluated in a Pediatric Oncology Group (POG) Phase I trial in children with refractory solid tumors. TMTX was administered intravenously daily x 5 every three weeks. Starting dose was 6.4 mg/m2/day. Dose was escalated by 20% until the maximal tolerated dose was reached. A total of 75 courses were administered to 26 children. The major toxicity was myelosuppression, of which neutropenia and thrombocytopenia were most prominent. Rash, mucositis, and transient liver enzyme elevations were infrequently seen. Responses were observed in children with brainstem glioma, neuroblastoma, and renal cell carcinoma. The recommended Phase II dose using this schedule is 9.2-11 mg/m2/day depending on how heavily the patient has been treated prior to initiating this therapy.

Adolescent↗
PubMed1993

Reoperative coronary artery bypass grafting without cardiopulmonary bypass.

Between June 1979 and January 1992, 46 men and 13 women aged 35 to 81 years (mean, 58 years) underwent reoperative coronary artery bypass grafting without cardiopulmonary bypass. Isolated reoperative circumflex bypass was performed through a left thoracotomy, and reoperative bypass to the right coronary artery and left anterior descending coronary systems was through a median sternotomy. Complete revascularization was the goal in all patients. Saphenous vein grafts were placed to the right coronary artery (n = 21), circumflex artery (n = 11), and left anterior descending artery (n = 24), and 14 internal thoracic artery to left anterior descending artery bypass grafts were performed. The overall mortality rate was 3.4% (2 deaths). Postoperative morbidity included myocardial infarction in 1 patient and pleuropulmonary complications in 6. No patient was reexplored for hemorrhage, and 19 patients required no blood products. Twenty patients underwent repeat coronary angiography, and 18 of 20 grafts placed without cardiopulmonary bypass were patent. At a mean follow-up interval of 42.2 months 35 of 50 evaluable patients were in functional class I or II. In selected patients, reoperative coronary artery bypass grafting can be performed without cardiopulmonary bypass with a low perioperative morbidity and mortality rate, satisfactory graft patency rates, and good long-term symptomatic improvement.

Adult↗
PubMed1993

The qualitative evaluation of the pharmacokinetics of subconjunctivally injected antifungal agents in rabbits.

Dutch-belted rabbits with corneal epithelium either intact or debrided were injected subconjunctivally with 300 microliters of one of six antifungal agents: 10 mg/ml miconazole, 5 mg/ml fluconazole, 5 mg/ml ketoconazole, 2.5 mg/ml itraconazole, and 5 mg/ml amphotericin B. At intervals of 10 min to 96 h after injection, animals were killed and corneas removed at the limbus. Three vertical strips from the right cornea and four contiguous 3-mm disks trephined from the central vertical axis of the left cornea were placed on agar plates seeded with an appropriate indicator organism. After 24 h of incubation, the zones of inhibition were measured. For itraconazole, miconazole, fluconazole, saperconazole, and ketoconazole, central corneal levels peaked by 2 h in normal and debrided corneas. Little or no drug was detectable after 4-8 h, except for itraconazole, which persisted in the cornea for at least 24 h in both normal and debrided corneas. Peak levels of amphotericin B in the central cornea were achieved after 2 h in rabbits with debrided corneas, with no drug activity measured after 8 h. There were no detectable levels of drug found in the central corneas of rabbits with intact corneal epithelium. On the basis of this pilot study, the method offers a rapid approach to the screening of antifungal agents for possible use by subconjunctival injection.

Animals↗
PubMed1992

Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses.

The ocular pharmacokinetics of saperconazole, an experimental lipophilic triazole with activity against filamentous fungi, including Aspergillus and Candida species, were evaluated in rabbits by radioassay. The drug was administered by topical, subconjunctival, and oral routes. Following a single 20-microL drop of 0.25% saperconazole in normal corneas, a mean (+/- SEM) peak level of 2.32 +/- 0.06 micrograms/g was achieved in 10 minutes. In débrided corneas, a peak level of 13.09 +/- 2.87 micrograms/g was achieved in 2 minutes. The drug was rapidly cleared from the cornea within 2 hours. The administration of 13 drops during 1 hour resulted in a threefold increase in normal corneal levels and in a sixfold increase in débrided cornea levels. Peak levels following subconjunctival injection in normal corneas (12.91 +/- 2.02 micrograms/g) were approximately twofold greater than those following sustained topical administration (6.19 +/- 0.16 micrograms/g) and, in débrided corneas, were a third higher than those following topical therapy in débrided corneas. Clearance was virtually complete by 8 hours. Levels following oral administration were low and probably subtherapeutic in all ocular tissues that were evaluated. Bioassay studies revealed that 44.17% of the drug in the cornea following topical administration was bioactive.

Administration, Oral↗
PubMed1992

Effect of light dose on the photodynamic destruction of endobronchial tumors.

The effects of various light power densities (milliwatts per centimeter of diffusing fiber [mW/cf]) and light doses (joules per centimeter of diffusing fiber [J/cf]) on the effectiveness of photodynamic therapy to endobronchial and tracheal tumors were evaluated at 46 different sites. All patients had squamous cell carcinoma or adenocarcinoma. They received 2 mg/kg body weight dihematoporphyrin ether intravenously 2 days before treatment bronchoscopy. Only one light treatment was delivered to the site. Patients were treated with diffusing cylinder light tips and underwent toilet bronchoscopy 2 days after photodynamic therapy. The percentage of obstruction was estimated before and after treatment and before and after toilet bronchoscopy. There was no difference between the effects resulting from power densities of 400 and 500 mW/cf, nor were there differences in the reactions between squamous cell carcinoma and adenocarcinoma. The amount of tumor that could be removed at the end of the treatment bronchoscopy, the amount of reobstruction by secretions and exudate seen at toilet bronchoscopy, and the final percent decrease in obstruction at the end of toilet bronchoscopy were proportional to the light dose. Because the final percentage decrease in obstruction plateaued at light doses of 400 to 500 J/cf and there was no statistically significant difference between 400 and 500 J/cf, we recommend using a power density of 500 mW/cf and a light dose of 400 J/cf during photodynamic therapy.

Adenocarcinoma↗
PubMed1992

Severe refractory anemia with ringed sideroblasts and bone marrow aplasia in a child.

Sideroblastic anemia is an extremely rare disorder in children. This report describes a 9-year 4-month-old girl with severe refractory anemia with ringed sideroblasts (RARS) that progressed to severe bone marrow aplasia. Ultrastructural studies revealed the presence of abundant intramitochondrial deposits of iron in erythroblasts similar to that observed in adults with this disorder. Although acid ferrocyanide staining confirmed the ferric valence of the iron deposits, they lacked morphologic and cytochemical characteristics associated with ferritin and hemosiderin. Bone marrow culture showed decreased or absent CFU-GEMM, CFU-GM, CFU-E, and BFU-E. Erythrocyte uroporphyrinogen I synthase, aminolevulinic acid dehydratase, uroporphyrinogen decarboxylase, urinary porphyrins, porphobilinogen, and aminolevulinic acid were normal. Free red cell protoporphyrin was increased. Therapy with corticosteroid and androgens was totally ineffective. The aplastic bone marrow in this child appeared to represent the end stage of RARS and differed from adults with RARS, who more frequently demonstrate a chronic course, often with the onset of leukemia as a terminal sequela. Although this case documents the occurrence of RARS in a child, additional reports of children with this disorder will be required to determine the prognosis and natural history of RARS in children.

Anemia, Sideroblastic↗