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C V Allen

Publications and source records attributed to C V Allen.

At least 19 recordsLinked to original sources

Comparison of cytosine arabinoside delivery to rat brain by intravenous, intrathecal, intraventricular and intraparenchymal routes of administration.

We evaluated the delivery of 14C-cytosine arabinoside (AraC) to rat brain by: 1) intravenous (IV) bolus, by 2) intrathecal (IT) and 3) intraventricular (IVT) infusion, and by 4) convection-enhanced delivery (CED) into the caudate nucleus. Plasma and brain AraC metabolites were measured with HPLC, and distribution and concentration of 14C-AraC in brain sections were measured by quantitative autoradiography. After IV administration, the alpha and beta plasma half-lives were 1.9 and 46.5 min, respectively. The blood-to-brain transfer constant of AraC was 2.5+/-1.4 microliter g(-1) min(-1), compatible with high water solubility. After IT and IVT administration, tissue levels were high at the brain and ventricular surfaces, but declined exponentially into brain. After CED, maximum brain levels were up to 10,000 times higher than the IV group, and the distribution pattern was one of high 14C-AraC concentration in the convective component, with exponentially declining concentrations outside this region. The rate loss constant from brain was 0.002+/-0.0004 min(-1), suggesting that AraC was accumulating in brain cells. AraC was metabolized into uracil arabinoside within the brain. 14C-AraC was infused into 1 dog and distributed widely in the ipsilateral hemisphere. These studies suggest that delivery of AraC to brain parenchyma by the IV, IT or IVT routes will be subtherapeutic. Delivery by CED can achieve, and maintain, therapeutic levels of AraC in the brain, and should be further evaluated as a potential method of drug delivery.

Animals↗

Comparison of 14C-sucrose delivery to the brain by intravenous, intraventricular, and convection-enhanced intracerebral infusion.

OBJECT: The authors evaluated convection-enhanced delivery (CED) of 14C-sucrose to the rat brain as a method of enhancing cerebral drug delivery and compared it with intravenous (i.v.) and intraventricular (i.v.t.) routes of administration. METHODS: Groups of rats received 14C-sucrose by bolus i.v. infusion, i.v.t. infusion for 1, 2, or 7 days at 0.17 microl/minute, or CED at rates from 0.01 to 0.5 microl/minute for periods from 1 hour to 7 days. Radioisotope distribution and concentration in tissue were analyzed using quantitative autoradiography. Intravenously administered sucrose reached the entire brain, but levels in tissue were low. After i.v.t. administration, sucrose levels in tissue were high at, and declined exponentially away from, the ventricular surface. Chronic CED administration maintained high levels of sucrose in tissue that focally were up to 10,000 times higher than in the i.v. group. The isotope distribution pattern after chronic CED infusions indicated a central component that resulted from convention and a peripheral component in gray matter that was the result of diffusion. The brain influx (0.42 microl/g/min) and diffusion constants of sucrose (2.8 x 10(-6) cm2/second) were similar to reported values. The total brain efflux constant was 0.0044 minute, whereas the blood-brain barrier (BBB) efflux constant was 0.0016 minute. There were no pathological changes in the brains after CED except those associated with cannula insertion. Sucrose, which was thought to be inert, was found to interact with brain tissue; up to 25% was bound to an unidentified tissue component. CONCLUSIONS: Chronic CED appears to be a potentially useful method for significantly circumventing the BBB and increasing delivery of water-soluble drugs to the brain.

Animals↗

Changes in blood-brain barrier permeability associated with insertion of brain cannulas and microdialysis probes.

Blood-brain barrier (BBB) transcapillary transport was studied after insertion of cannulas and microdialysis probes into the brains of three groups of rats. Quantitative autoradiography was used to measure changes in BBB permeability around the insertion site. In the first group, BBB function was measured with 14C-sucrose at times from immediately, and up to 28 days, after insertion of a microdialysis probe. BBB function was disrupted biphasically: a 19-fold increase in the influx constant (K1) of sucrose occurred immediately after insertion with a second 17-fold increase at 2 days, followed by a slow decline to 5 times normal values at 28 days. In the second group, 14C-dextran (70 kDa) was used to measure BBB transcapillary transport; K1 was increased 90-fold after probe insertion. In the 3rd group, 14C-AIB (alpha-aminoisobutyric acid) was used to evaluate BBB transport after insertion of a 27 gauge cannula, which was used to infuse 1 microliter of saline over 5 min. The K1 of AIB was increased 25 times control values. We conclude that BBB transcapillary transport function is disturbed in response to insertion of brain cannulas and/or microdialysis probes, that BBB dysfunction is maximal at the cannula or probe tip, varies with time after insertion, may persist for at least 28 days after insertion, and occurs over a wide molecular range of solutes. These results suggest caution when using microdialysis as a method to study normal BBB function, and suggest that microdialysis may overestimate the rate of transfer into and out of the brain.

Animals↗

Art in nursing.

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Art↗

Anterior resection and primary anastomosis following high dose preoperative irradiation for adenocarcinoma of the recto-sigmoid.

Preoperative irradiation for adenocarcinoma of the rectum and sigmoid does not always limit the surgery to an abdominoperineal resection. From 1960 to 1976 anterior resection and primary anastomosis of the bowel has been performed in 13 patients with adenocarcinoma of the rectum and sigmoid whose tumor had been irradiated with 5000 rads with small pelvic fields. The inferior surgical resection line was within or very near the edge of the radiation field in 10 patients. In no instance was the superior resection line irradiated. Compared to a group of 79 patients treated with anterior resection only, the preoperatively irradiated patients had lower incidence of pelvic and anastomotic tumor recurrence, but a higher incidence of anastomotic leak and subsequent adhesions and intestinal obstruction. We stress that if irradiated rectum is considered for forming the anastomosis, a temporary "protective colostomy" should be strongly considered at the time of the surgery.

Adenocarcinoma↗

Limited epithelial carcinoma of the ovary treated with curative intent by the intraperitoneal installation of radiocolloids.

Between January 1960 and September 1972, 104 patients with limited epithelial carcinoma of the ovary received intraperitoneal radiocolloid. Fifty-six of these patients also received external beam radiation therapy to the pelvis (pelvic RT). Five-year actuarial no-evidence-of-disease survival rates were 95% for stage Iai, 82% for Iaii, 73% for Ib, 67% for Ic, 67% for IIa, 67% for IIb without gross residual tumor (GRT), 25% for IIb with GRT, and 50% for III with minimal or no GRT. The addition of pelvic RT following radiocolloid could not be shown to affect survival of patients with Stage I and IIa tumors. Small bowel complications were related to the use of pelvic RT, however, occurring in 2.2% of patients treated with radiocolloid alone and 24% of patients treated with colloid and pelvic RT (p less than 0.005). In patients who underwent abdominal surgery following treatment of ovarian cancer, no excessive complication rate was observed. We conclude that for patients with stages Iaii through IIa, postoperative radiocolloid appears to provide the greatest chance of survival with the least chance of complication. For patients with Stage IIb and III lesions in whom there is minimal or no GRT, radiocolloid followed by pelvic RT produced survival rates comparable or superior to any other form of postoperative therapy.

Adult↗

Preoperative radiotherapy for adenocarcinoma of the rectosigmoid.

Ninety-seven patients with adenocarcinoma of the rectosigmoid have been treated with high dose (5000-6000 rad) preoperative irradiation from 1960 through 1972 at the University of Oregon Health Sciences Center. Fifty-seven were initially clinically resectable and 40 were initially inoperable. Forty of the 57 initially clinically resectable patients had "curative" resections and are at risk for more than 5 years. An increase in 5-year survival (from 38% to 53%) and an absence of pelvic recurrence have occurred in those patients receiving preoperative irradiation and "curative" resection. Four of the 40 initially inoperable patients are alive without tumor. Three of the four survivors had irradiation and surgery; one had irradiation only. An additional four patients had no evidence of tumor at death. Tumor was totally sterilized by irradiation and nine patients and reduced to microfocal extent in an additional three of the 97 patients. Incidence of complications was no greater than has been reported in a surgical series from the same institution.

Adenocarcinoma↗

A new head holder for reducing axial movement and repositioning errors during physiological CT imaging.

OBJECTIVE: We designed a new head holder for immobilization and repositioning in dynamic CT studies of the brain. MATERIALS AND METHODS: A customized thermoplastic face mask and foam head rest were made to restrict movement of the head in all directions, but particularly out of the axial plane (z-movement). RESULTS: This design provided a rigid, detailed mold of the face and back of the head that minimized motion during lengthy CT studies and enabled accurate repositioning of the head for follow-up studies. Markers applied directly to the skin were used to quantify z-movement. CONCLUSION: When tested on 12 subjects, immobilization was limited to < 2.0 mm under worst-case conditions when the subject was asked to attempt forced movements. Repositioning was accurate to < 1.5 mm when the subject was removed from the head holder and then placed back into it.

Brain↗

Noninvasive measurement of arterial blood plasma concentration of iodinated contrast agents from CT scans of human brain.

OBJECTIVE: Our goal was to assess the accuracy of estimating the time course of the arterial plasma concentration of meglumine iothalamate from cranial CT images of different vascular structures in the brain. MATERIALS AND METHODS: Dynamic CT studies of transcapillary transport in various brain lesions were analyzed. Vascular structures in the brain were identified and classified in three categories: arteries, veins, and venous sinuses. Systemic venous blood samples were taken prior to the infusion of meglumine iothalamate and 10 min after completion of the infusion and used as a calibration for the volume averaging fraction of the image of each vascular structure. A time course of plasma meglumine iothalamate concentration for each of the vascular categories in the CT images was obtained and compared with a variety of methods. RESULTS: Significant differences were found for measurement of plasma meglumine iothalamate concentration from different vascular categories. There was also a disparity between the volume averaging fraction that we calculated and what would be expected due to the measured systemic hematocrit for all vascular structures. CONCLUSION: The use of images of veins and venous sinuses consistently underestimated the arterial concentration around the peak values. Correcting the imaged venous sinus values with the measured systemic hematocrit was even less reliable. The most accurate method of determining arterial plasma concentration of meglumine iothalamate from CT images of brain was to correct the identified arterial vessels for volume averaging.

Brain↗