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Biomedical subjects

A G Meek

Publications and source records attributed to A G Meek.

36 records · Page 2Linked to original sources

Preoperative preparation of high-risk, specifically hyperimmunized canine renal allograft recipients with total-lymphoid irradiation and cyclosporine.

Hyperimmunized subjects are a particularly high-risk and rapidly growing group in the patient population awaiting renal transplantation. In a search for methods designed to ameliorate the prognosis in such cases, dogs of defined DLA genotype were sensitized with DLA incompatible skin allografts and injections of buffy coat. Each recipient was challenged with a renal allograft bearing the same DLA incompatibilities. Five dogs received kidney transplants, without any other treatment, and rejected their transplants at 2.5, 4, 5, 6, and 6.5 days, respectively. Another four dogs were given a 9-11-week course (1760 +/- 35 cGy) of total-lymphoid irradiation (TLI), followed by rabbit antithymocyte globulin (ATG); these animals rejected their renal allografts at 7, 8, 14, and 17 days, respectively. Five other dogs were treated with TLI and received cyclosporine (CsA) and methylprednisolone (MPd) daily until graft rejection. Their renal allografts survived for 7.5, 8.5, 20, 62, and 227 days, respectively. Renal allografts placed in normal recipients under the same conditions of donor-recipient DLA incompatibility had a mean survival time of 12.4 days (range: 10-18 days). At the time of transplantation, the specific anti-DLA antibody titers in the recipients were 81 to 243 in the untreated dogs; 27 to 81 in the TLI-ATG-treated group, and 3 to 243 in the TLI-CsA/MPd-treated group. The titers fell within 24-48 hr after renal transplantation, to 3 to 81 in the untreated sensitized dogs; they were 3 to 9 in the TLI-ATG-treated group, and were 9 to 243 in the TLI-CsA/MPd treated group. The cytotoxic antibody titers reached postoperative peaks of 6500 to 200,000 in the untreated dogs; 729 to 6500 in the TLI-ATG-treated dogs, and 243 to 6500 in the TLI-CsA/MPd-treated recipients. The combined use of TLI and CsA/MPd can significantly inhibit the capacity of immunized recipients to muster a secondary humoral response to the DLA antigen(s) used in the sensitization process; such treatment also abrogates the ability of the recipients to reject renal allografts bearing the same DLA specificities in accelerated fashion. This effect of TLI and cyclosporine may be of relevance to current severe problems in high-risk hyperimmunized human renal transplant candidates.

Animals↗

Concurrent radiochemotherapy in advanced breast cancer.

An initial trial to determine whether the theoretical advantage of concurrent systemic chemotherapeutic protection and local control (by radiation) could be achieved has been applied to 16 patients with breast cancer (Stage 3 and 4). CMFP/CMF combination chemotherapy has been administered with external irradiation (5000 rad breast, 4000-4400 rad nodes). External irradiation was successfully accomplished with tangenital fields to avoid combined modality esophagitis while achieving internal mammary node irradiation. Six patients subsequently received Iridium-192 interstitial implantation. Six patients treated preoperatively (4000 rad, breast) were able to have modified mastectomy within 3-6 weeks of completing radiation therapy without graft requirement or undue morbidity. Acute reactions during therapy included some amplification of epidermitis and myelosuppression. Prolongation of the radiation treatment course occurred in two patients and delay in chemotherapy cycles in four patients. In two patients, the leukocyte count nadir was below 1000 and one was hospitalized with fever. The majority of the patients achieved 75% of the designed chemotherapeutic doses in the ensuing year. Many of the patients with advanced disease were administered an Adriamycin-containing regimen upon completion of the radiation therapy. The current results suggest that it would be feasible to initiate a randomized prospective study using these techniques to compare sequential and concomitant chemo-radiation therapy in primary breast cancer to determine whether there is significant advantage in local control and duration of NED survival in either of the treatment regimens.

Adult↗

Carcinoma of the colon: irradiation by delayed split whole-abdominal technique.

Locally advanced and recurrent colon cancer was treated by irradiating first the pelvis and two hours later the upper abdomen. Curative treatment consisted of 4,000-5,000 rad (40-50 Gy) in 200-rad (2-Gy) fractions to the pelvis and 3,000 rad (30 Gy) in 150-rad (1.5-Gy) fractions to the upper abdomen. Palliative treatment consisted of 2,100 rad (21 Gy) in 300-rad (3-Gy) fractions to the liver, 3,000 rad (30 Gy) in 150-rad (1.5-Gy) fractions to the upper abdomen, and 4,000-5,000 rad (40-50 Gy) in 200-rad (2-Gy) fractions to the pelvis. Treatment was tolerated well, and acute toxicity was limited. Seven of the 11 patients treated curatively remain free of abdominal disease after 10-35 months; median survival among 9 patients treated palliatively was 9 months.

Abdomen↗

Spontaneous pneumothorax during adjuvant chemotherapy for soft-tissue sarcoma.

A 21-year-old man with fibrosarcoma of the left thigh, treated with adjuvant chemotherapy following surgery and radiation, presented with bilateral spontaneous pneumothoraces as the initial manifestation of metastatic disease. While the pathogenesis of this condition is uncertain, it is possible that in this patient drug-induced necrosis of peripherally located subclinical metastatic pulmonary nodules led to spontaneous pneumothorax.

Adult↗

Digoxin -- quinidine interaction.

A patient with chronic paroxysmal atrial fibrillation, receiving maintenance doses of digoxin, was admitted for addition of quinidine therapy. With stable serum digoxin levels, the institution of oral quinidine sulfate resulted in a rise in the serum digoxin level in less than 24 hours. The serum digoxin concentration increased more than threefold before digoxin was discontinued. The rise and fall of the digoxin serum concentration appeared to correlate directly with an increase and decrease in the PR interval. With the reinstitution of digoxin at lower doses, apparently stable therapeutic levels of both digoxin and quinidine were achieved. However, discontinuation of quinidine alone was followed by a prompt fall in the serum digoxin level. This study demonstrates that quinidine produces a significant increase in the serum digoxin level. The increased digoxin concentration appears to correlate with enhanced electrophysiologic effects of digoxin and emphasizes the caution required when these two drugs are used simultaneously.

Atrial Fibrillation↗

Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy: a preliminary study.

PURPOSE: Our goal was to measure the effect of radiotherapy on the brain glucose metabolism of tumoral and nontumoral tissue of patients with brain malignancies. METHOD: Fifteen patients with primary or metastatic brain tumors were studied with 2-deoxy-2-[18F]fluoro-D-glucose and PET prior to radiotherapy, and nine of them were rescanned 1 week after completing radiotherapy. RESULTS: Brain metabolism in patients (all brain regions except for tumoral and edematous tissue) was lower than that of matched controls (34.0 +/- 8.3 vs. 46.5 +/- 6.4 mumol/100 g/min; p < or = 0.0001). Five of the nine patients retested after radiotherapy showed decrements in tumor metabolism (47 +/- 10%; p < or = 0.05) and increases in brain metabolism (10 +/- 4%; p < or = 0.004), and the other four showed no changes in tumor or in brain metabolism. Radiotherapy-induced changes in tumor metabolism were negatively correlated with changes in brain metabolism (r = 0.85, p < or = 0.004), but not with changes in tumor volume (assessed with MR images). CONCLUSION: The study indicates that radiotherapy-induced increases in metabolism of nontumoral tissue are secondary to decreased tumor metabolic activity and not just due to volume reduction.

Adult↗

Continuous three-dimensional radiation dosimetry in tissue-equivalent phantoms using electron paramagnetic resonance in L-alpha-alanine.

A new tissue-equivalent phantom material has been developed which also acts as a dosimeter. The new phantom material has a similar elemental composition to that of soft tissue and has a density 1.1 g/cm3. The phantom has an agar-gel base, and contains crystallized L-alpha-alanine which traps radiation-induced free radicals. Samples from the phantom were analyzed by an electron paramagnetic resonance (EPR) spectrometer and the intensity of the EPR signal was related to the absorbed dose. When calibrated, the phantom material acts as a dosimeter, with applications in radiation therapy.

Alanine↗

Tests of an electron monitor for routine quality control measurements of electron energies.

The depth dose for electrons is sensitive to energy and the AAPM Task Group 24 has recommended that tests be performed at monthly intervals to assure electron beam energy constancy by verifying the depth for the 80% dose to within +/- 3 mm. Typically, this is accomplished by using a two-depth dose ratio technique. Recently, a new device, the Geske monitor, has been introduced that is designed for verifying energy constancy in a single reading. The monitor consists of nine parallel plate detectors that alternate with 5-mm-thick absorbers made of an aluminum alloy. An evaluation of the clinical usefulness of this monitor for the electron beams available on a Varian Clinac 20 has been undertaken with respect to energy discrimination. Beam energy changes of 3 mm of the 80% dose give rise to measurable output changes ranging from 1.7% for 20-MeV electron beams to 15% for 6-MeV electron beams.

Electrons↗

Energy response of agar-alanine free radical dosimetry to therapeutic electron beams.

Calculations of the energy response of an agar-alanine phantom dosimeter (AAPD) to electrons in the energy range of 0.15-20 MeV together with experimental results at 16 MeV are presented. It is shown that the sensitivity of the EPR dosimeter (EPR signal/Gray) is independent of alanine crystal size and varies less than 2%, in the electron energy range indicated. Thus, the measured free radical density distribution may be used directly as an indication of the absorbed dose distribution in an irradiated phantom.

Agar↗

Cytologic and histologic changes in irradiated loops of transplanted small bowel.

The histopathologic and cytopathologic changes in irradiated transplanted loops of bowel were assessed in 10 dogs. Five received conventional radiotherapy (CRT), and five received hyperfractionated doses of radiotherapy (HFRT) over the same period. Both groups exhibited identical cytologic findings, including blunting of villi and significant crypt atypia that could be mistaken for malignancy. Histologic examination corroborated the cytologic findings. At the end of the experiment two of the dogs that received CRT had developed strictures. One showed extensive submucosal fibrosis, while the other showed submucosal atrophy.

Animals↗