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Biomedical subjects

J C Andrews

Publications and source records attributed to J C Andrews.

At least 55 records · Page 3Linked to original sources

Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up.

UNLABELLED: The treatment of hepatic tumors remains unsatisfactory. These lesions receive most of their blood supply from the hepatic artery, therefore the hepatic artery administration of beta-emitting particulate radiopharmaceuticals is an attractive approach to deliver therapeutic irradiation to the liver and differentially to tumors within the liver. METHODS: A Phase I dose escalation study of the hepatic tolerance to radiation delivered by 90Y containing glass microspheres was carried out in 24 patients with hepatic malignancy. Doses of 90Y microspheres to achieve an estimated whole-liver nominal absorbed radiation dose of 5000 cGy (two patients), 7500 cGy (six patients), 10,000 cGy (seven patients), 12,500 cGy (six patients), and 15,000 cGy (three patients) were administered via the hepatic artery. The administered nominal absorbed radiation dose (NARD) was estimated based on liver volume determined from CT scans and the assumption of uniform distribution of microspheres throughout the liver. RESULTS: No hematologic, hepatic or pulmonary toxicity was encountered in the dose range examined during a mean follow-up period of up to 53 mo. Reversible gastritis or duodenitis was encountered in four patients without imaging or biopsy evidence for extrahepatic deposition of microspheres. Response data, based on CT scans obtained 16 wk after treatment, showed progressive disease in eight patients, stable disease in seven patients, minimal response in four patients and partial response in five patients. Subsequent follow-up revealed three long-term survivors at 204, 216 and 228 wk. CONCLUSIONS: These preliminary data demonstrate that in the examined dose range, radiation may be safely delivered to liver tumors by means of 90Y glass microspheres with encouraging response data.

Adult↗

Stereolithographic model construction from CT for assessment and surgical planning in congenital aural atresia.

Surgical planning for the treatment of congenital aural atresia has depended greatly on the use of high resolution computerized tomography (CT) and, recently, three-dimensional CT for visual representation of the complex anatomy associated with this condition. Computerized plastic model construction, stereolithography, allows the digital data obtained through CT scanning to produce a life-size anatomically accurate plastic model of the structure scanned. When this technique is applied to congenital aural atresia there is good bony surface rendering as well as complete representation of the deeper structures contained within the temporal bone, including the middle ear cleft, ossicular mass, and fallopian canal. The surgeon can use this model to augment imaging in becoming familiar with the patient's unique anatomy and to practice a planned surgical procedure.

Adolescent↗

Preparation of the human skull for skull base anatomic study.

Human skulls are unsurpassed in the ability to provide three-dimensional instruction in osteology as well as understanding the sites of soft tissue insertion and the intricate course of neurovascular structures in the skull base. Recent geopolitical developments in Asia have led to extreme difficulty in obtaining human skull specimens. The purpose of this article is to present a method for the preparation of dried human skulls from fresh and frozen cadavers using commonly available chemicals. The technique, requiring about 8 weeks total time and basic equipment, consists of maceration accelerated by several enzymes followed by defatting, washing, and bleaching. The skulls produced are of excellent quality and durability with no preparation artifacts. An economical source of skulls has now been reestablished to facilitate learning of the intricate relationships of the skull base.

Journal Article↗

Hepatic parenchymal changes after intraarterial Y-90 therapy: CT findings.

The serial contrast material-enhanced computed tomographic scans of 23 patients treated with intraarterial yttrium-90 microspheres as therapy for hepatic metastatic disease were reviewed for evidence of parenchymal changes in the liver in areas not involved with tumor. Irregular low-attenuation geographic areas that developed in the hepatic parenchyma after therapy were graded as mild, moderate, or severe and were evident in 12 of 23 patients. In nine cases of mild to moderate changes in the hepatic parenchyma, the abnormality was either focal or asymmetric. In all three patients receiving the highest dose (15,000 cGy), severe diffuse parenchymal changes were seen in all hepatic segments. In the remaining 11 patients, no parenchymal changes were seen. The most pronounced changes were seen at 8 weeks after therapy and were partially or completely reversible at 16-24 weeks. All patients had minimal or no change in liver function and no clinical sequelae attributable to liver injury.

Adult↗

Treatment of primary hepatobiliary cancers with conformal radiation therapy and regional chemotherapy.

PURPOSE: To develop more effective regional therapy for patients with unresectable primary hepatobiliary cancer using concurrent conformal radiation therapy and intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd). PATIENTS AND METHODS: Twenty-six patients with unresectable, nonmetastatic primary hepatobiliary cancer were treated with concurrent IAH FdUrd (0.2 mg/kg/d) and conformal hepatic radiation therapy (1.5 to 1.65 Gy per fraction twice per day). The total dose of radiation administered to the tumor depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for toxicity, hepatobiliary relapse, and survival; 17 patients were assessable for response (eight had cholangiocarcinoma not assessable by computed tomographic [CT] scan and one progressed distantly during treatment). The median potential follow-up duration was 27 months. RESULTS: Whole-liver radiation was administered to six patients with diffuse hepatocellular carcinoma (HCC). Eleven patients with localized HCC and nine with cholangiocarcinoma received focal radiation to a dose of 48 to 72.6 Gy. An objective response for assessable patients was observed in 11 of 11 patients treated with focal radiation, but only one of six patients treated with whole-liver radiation. Whole-liver radiation accounted for five of seven patients with > or = grade 3 toxicity and four of six local treatment failures. Two patients had nonfatal radiation hepatitis. The median survival duration for patients with localized hepatobiliary cancer was 19 months, while patients with diffuse HCC had a median survival duration of 4 months. The rate of actuarial freedom from hepatobiliary progression in patients with localized disease was 72% at 24 months. CONCLUSION: These findings suggest that three-dimensional planned focal liver radiation and IAH FdUrd can produce a high, durable response rate and an encouraging median survival duration in patients with nondiffuse, unresectable primary hepatobiliary cancer.

Actuarial Analysis↗

Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case-control study. The VA Cooperative Study Group.

A case-control study of patients with progressive (cases) or nonprogressive (controls) disease was designed to determine the association among disease progression, zidovudine sensitivity, and syncytium-inducing phenotype. Viral isolates were screened for sensitivity to zidovudine using a peripheral blood mononuclear cell-based assay and for syncytium-inducing (SI) phenotype in MT2 cell culture. Thirty-four patients, whose disease progressed to AIDS or whose CD4 cell numbers fell < 200 cells/mm3, were matched with 34 patients whose conditions had not progressed or whose CD4 cell numbers remained > 200 cells/mm3. Virus was successfully cultured from both the progressor and the nonprogressor in 17 of these 34 matched case-control pairs. In six of the 17 pairs, virus isolated from the progressor had an IC50 (50% inhibitory concentration) for zidovudine > 1 microM and at least threefold greater than the IC50 of virus isolated from the matched nonprogressor (p = 0.04). In 16 of these 17 pairs the virus isolated from the progressor had the SI phenotype, indicative of high cytopathogenicity, while the virus from the matched nonprogressor had a non-syncytium-inducing phenotype (p < 0.0001). Zidovudine therapy did not appear to select for the SI phenotype in this patient population. A statistically significant association between high-level zidovudine resistance and clinical disease progression was demonstrated. A statistically significant association between the SI phenotype and disease progression was demonstrated. The results suggest that disease progression while being treated with zidovudine therapy may be more closely associated with the SI phenotype than with zidovudine resistance.

Acquired Immunodeficiency Syndrome↗

The exacerbation of symptoms in Menière's disease during the premenstrual period.

The pathophysiology of the characteristic episodic symptoms of vertigo, low-frequency hearing loss, and tinnitus in Menière's disease remains poorly understood. It is likely that the manifestation of this condition may be multifactorial and related to elements affecting the inner ear beyond the underlying pathology of endolymphatic hydrops. We have identified a subgroup of female patients with Menière's disease in which the symptoms of this disorder are correlated with the late luteal phase of the menstrual cycle (premenstrual period). Through audiometric and vestibular testing, we have documented these inner ear effects in six women. Although many hormonal effects occur during the premenstrual period, compartmental fluid redistribution within the body may be the most pertinent. Endolymphatic hydrops represents a fluid imbalance within the inner ear and, when combined with an additional fluid shift, may produce symptomatic dysfunction. Case histories demonstrating the correlation of the symptoms of Menière's disease and the premenstrual period will be presented along with theoretical mechanisms of pathophysiology.

Adolescent↗

Sperm capacitation in the domestic cat (Felis catus) and leopard cat (Felis bengalensis) as studied with a salt-stored zona pellucida penetration assay.

The ability of domestic cat or leopard cat spermatozoa to penetrate zonae pellucidae (ZP) of salt-stored, domestic cat oocytes was examined as an assay for sperm capacitation. Ovarian oocytes were recovered after ovariectomy and matured in vitro for 18-36 h. Following removal of cumulus cells, the oocytes were used fresh, or stored (4 degrees C, 0.5-24 weeks) in a HEPES-buffered hypertonic salt solution. Electroejaculated, washed sperm (2-4 x 10(6) sperm/ml) were preincubated for 1.0 h (38 degrees C, 5% CO2 in air) and then co-incubated (2 x 10(5) sperm/ml) with fresh or stored oocytes for 6.0 h. Gametes were incubated in a protein-free, modified Tyrode's solution (TLP-PVA) or in the same medium containing 4.0 mg/ml bovine serum albumin (BSA; TALP-PVA). Treatments were compared for percentage ZP penetration (defined as sperm heads reaching more than halfway through the ZP) as an index of sperm capacitation. In both the domestic cat and leopard cat, there was no difference (P greater than 0.05) in sperm penetration of fresh ZP (domestic cat, 42.5 +/- 5.4%; leopard cat, 38.6 +/- 2.8%) or stored ZP (domestic cat, 32.4 +/- 4.2%; leopard cat, 27.6 +/- 2.3%). Sperm incubated in protein-free medium (TLP-PVA) were less capable (P less than 0.05) of ZP penetration (domestic cat, 14.6 +/- 5.9%; leopard cat, 7.9 +/- 3.0%) than sperm incubated in medium TALP-PVA containing BSA (domestic cat, 60.3 +/- 5.9%; leopard cat, 58.4 +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The use of 3-D dose volume analysis to predict radiation hepatitis.

Although it is well known that the tolerance of the liver to external beam irradiation depends on the volume of liver irradiated, few data exist which quantify this dependence. Therefore, a review was carried out of our clinical trial for the treatment of intrahepatic malignancies in which the dose of radiation delivered depended on the volume of normal liver treated. Three dimensional treatment planning using dose-volume histogram analysis of the normal liver was used for all patients. Nine of the 79 patients treated developed clinical radiation hepatitis. None of the patient related variables assessed were associated with radiation hepatitis. All patients who developed radiation hepatitis received whole liver irradiation, as all or part of their treatment, which produced a mean dose greater than or equal to 37 Gy. Dose volume histograms were used to calculate normal tissue complication probabilities based on parameters derived from the literature. The risk of complication was greatly overestimated among patients receiving a high dose of radiation to part of the liver without whole liver treatment. An estimation of model parameters based on the clinical results indicated a larger magnitude for the "volume effect parameter" than the literature estimate (n = 0.69 +/- 0.05 vs 0.32; p less than 0.001). Computation of the normal tissue complication probabilities using the larger value of n produced a good description of the observed risk of radiation hepatitis. These findings suggest that dose volume histogram analysis can be used to quantify the tolerance of the liver to radiation. The predictive value of this parameterization of the normal tissue complication probability model will need to be tested with liver tolerance and dose volume histogram data from an independent clinical trial.

Adult↗

Design and testing of a high-flow autoperfusion catheter: an experimental study.

An autoperfusion catheter is similar to an angioplasty balloon catheter with side holes in the guide-wire lumen proximal to the balloon. When the balloon of the autoperfusion catheter is deployed and inflated in an artery, the guide wire is removed, and the hub of the guide-wire lumen is capped. The catheter then allows passive distal perfusion by using ambient pressure to drive blood into the guide-wire lumen, through the balloon, and out the end hole. This article discusses the requirements and constraints of a high-flow autoperfusion catheter, summarizes attempts to modify standard angioplasty catheters for use as an autoperfusion catheter, and describes the design and testing of a custom autoperfusion catheter capable of delivering approximately 3 mL/sec at physiologic pressures. In a model of canine acute renal artery occlusion lasting 90 minutes, the custom autoperfusion catheter provided marked protection from acute tubular necrosis compared with conventional percutaneous transluminal angioplasty catheters. The authors conclude that the high-flow autoperfusion catheter may be useful as a temporary stent in cases of rupture, dissection, or penetrating wounds involving large arteries.

Angioplasty, Balloon↗

Magnetic resonance imaging-guided fine needle aspiration for the diagnosis of skull base lesions.

Magnetic resonance imaging (MRI)-guided fine needle aspiration was used to obtain tissue from lesions of the skull base for cytologic diagnoses in 14 patients. Our technique utilized a guiding system to enable three-dimensional orientation in a two-dimensional scan and a high nickel content 22 gauge needle to minimize significantly MRI artifact. Needle access to the skull base was provided through a subzygomatic or retromandibular approach. In seven of nine cases an accurate diagnosis was established by this technique and later confirmed by surgical exploration and histologic analysis. Failure to obtain a representative specimen from the lesion occurred in one case and difficulty in interpreting the cytologic features of the tissue was encountered in another case. The indications, limitations, and technical details of the procedure are described.

Journal Article↗

Early predictors of survival in symptomatic HIV-infected persons treated with high-dose zidovudine.

The survival times of 246 patients treated with high-dose zidovudine beginning in 1986 were obtained through November 1988. We analyzed clinical and laboratory predictors of survival as measured before initiation of therapy and during the first 32 weeks of therapy. In a multivariate proportional-hazards model, we found significant independent predictive abilities for four pretherapy measurements (AIDS versus ARC diagnosis, Karnofsky performance score, age, and hemoglobin) and four measurements made during therapy (change in log CD4 lymphocyte count from pretherapy to week 24, CD8 lymphocyte count at week 24, rate of decline of hemoglobin over the first 3 months of therapy, and rate of decline in white blood count over the first 6 months of therapy). The presence of three predictors measured during therapy that are statistically significant when controlled for changes in CD4 count suggests that the use of other measures in addition to CD4 counts may substantially improve the prediction of long-term survival based on early response of surrogate markers to therapy.

Drug Administration Schedule↗

Three-dimensional CT scan reconstruction for the assessment of congenital aural atresia.

Major advances in medical computer graphics workstations have provided the capability to produce high quality three-dimensional image reconstructions from conventional thin-section computerized tomography (CT) scans with the ability to observe the imaged structure from any angle, with views and dimensions that are comparable to actual dissections. We have applied this technique to the temporal bone to assess congenital aural atresia in surgical planning for hearing reconstruction in six patients. The digital information produced by thin-section CT scanning allowed for the re-creation of multiplanar reformatted, shaded surface, and volumetric images. With this technique the surface landmarks of the temporal bone were readily visualized, the configuration of the atretic plate and middle ear in relation to the tegmen and glenoid fossa could be precisely assessed and the structure of the ossicular mass was easily analyzed. Most significantly, the facial nerve could be accurately and easily envisioned in its entire intratemporal course. Three-dimensional imaging is a highly desirable means for observing CT scan data to facilitate the surgical planning for correction of congenital aural atresia.

Adolescent↗

Treatment of cancers involving the liver and porta hepatis with external beam irradiation and intraarterial hepatic fluorodeoxyuridine.

A Phase I/II clinical trial was designed for patients with malignancies of the liver and porta hepatis. This protocol employed three concepts: a) boost treatment to gross tumor within the liver for selected patients, determined by the dose-volume histogram (DVH) of the normal liver that would be irradiated by boost treatment; b) concurrent use of intraarterial hepatic 5-fluorodeoxyuridine (FdUrd) as a radiosensitizer; and c) hyperfractionation (1.5 Gy fractions given bid greater than 4 hr apart). This report describes the results of treatment of the first 33 patients entered onto this study, with a minimum follow-up of 1 year. Twenty patients received only whole liver irradiation (33 Gy). Thirteen patients were treated with whole liver irradiation (30 Gy) plus a 15 Gy (6 patients) or 30 Gy (7 patients) boost (total 45 Gy and 60 Gy to the tumor, respectively). Forty-eight percent of the evaluable patients (14/29) had an objective response, based on CT scan. The median duration of response was 8 months. The chief toxicities were fatigue, nausea, gastritis, and diarrhea, which were less than or equal to grade 2 in severity. Two patients developed mild radiation hepatitis which was treated successfully with diuretics. These data suggest that the treatment of intrahepatic malignancies can be guided by the concept of DVH analysis of the normal liver to allow the safe administration of doses of radiation that are potentially tumoricidal and are well above those that would be predicted to be tolerable for the whole liver.

Adenoma, Bile Duct↗