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Biomedical subjects

S Wallace

Publications and source records attributed to S Wallace.

At least 109 records · Page 6Linked to original sources

Synthesis and evaluation of water-soluble polyethylene glycol-paclitaxel conjugate as a paclitaxel prodrug.

Water-soluble paclitaxel may cause less side effects and be less costly to administer in comparison to a taxol formulation using a cremophor EL/alcohol vehicle. In this study, polyethylene glycol (PEG; MW 5000) was conjugated to the 2' position of paclitaxel through a spacer succinyl group. PEG-paclitaxel as a non-ionic paclitaxel prodrug was highly water soluble (> 20 mg equiv. paclitaxel/ml). The release of paclitaxel from phosphate-buffered solution was pH dependent. The half-life of PEG-paclitaxel was 7.6, 54 and 311 min at pH 9.0, 7.4 and 6.0, respectively. PEG-paclitaxel inhibited the growth of B16 melanoma cells to an extent similar to that of paclitaxel. In MCA-4 mammary tumor-bearing mice, a single dose of PEG-paclitaxel (40 mg equiv. paclitaxel/kg body weight) significantly delayed tumor growth. The average number of days for the tumor to reach 12 from 8 mm in diameter increased from 6.5 days for control animals to 8.5 days for PEG-paclitaxel-treated animals and 9.4 days for paclitaxel-treated animals. These studies demonstrated that PEG may be used as an effective solubilizing carrier for paclitaxel.

Animals↗

Evaluation of [131I]iodoerythronitroimidazole as a predictor for the radiosensitizing effect.

The aim of this study was to evaluate whether radiolabeled iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140 and 240 min after the i.p. injection of IETNIM. After the irradiation, tumor growth assays were conducted and the effect of IETNIM as a radiosensitizer was estimated as enhancement factor (EF). Tumor uptake was measured at 35, 70, 140 and 240 min after i.p. injection of [131I]IETNIM, which were the same intervals used in the radiosensitization study. EF of IETNIM in mice treated with 25, 30 and 37 Gy irradiation was 0.72, 0.98 and 1.28, respectively. EF of IETNIM in mice irradiated at 35, 70, 140 and 240 min after the injection was 1.50, 1.69, 1.46 and 1.08, which corresponded to the tumor uptake and blood clearance of [131I]IETNIM. [131I]IETNIM may be a suitable radiopharmaceutical to predict the radiosensitization effect of misonidazole analogs on tumors.

Animals↗

Effects of nifedipine, metronidazole, and nitric oxide donors on spore germination and cell culture infection of the microsporidia Encephalitozoon hellem and Encephalitozoon intestinalis.

Two species of microsporidia, Encephalitozoon hellem and Encephalitozoon intestinalis, were isolated from AIDS patients and cultured in green monkey kidney cells. A spore germination assay and a cultured-cell infection assay were used to test the efficacy of candidate antiparasitic agents. The calcium channel blocker nifedipine, metronidazole, and two nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, were tested in the two assays. Nifedipine (10(-8) M) significantly inhibited E. hellem spore germination in three of four germination media. Metronidazole (10(-5) M) inhibited germination weakly and significantly inhibited E. intestinalis germination in a single germination medium. The inhibitory effect of nifedipine and metronidazole used together was greater than the sum of the effects of the drugs used alone in all E. hellem germination assays. The NO donors also inhibited spore germination. The inhibitory effect of nifedipine and metronidazole could be reversed by washing the spores, while that of the NO donors was not reversible. In early cultured-cell infections, both nifedipine (10(-8) M) and metronidazole (10(-5) M) significantly reduced the number of cells being infected. As the infection spread, these agents were less effective. Some inhibition of the spread of the infection was also demonstrated with the NO donors at a concentration (10(-5) M) not obviously toxic to the cultured cells. These data suggest that combination drug therapy targeting spore germination and intracellular parasite development is promising.

Acquired Immunodeficiency Syndrome↗

Changing demographics and state fiscal outlook: the case of sales taxes.

"Broad-scale demographic changes have implications for state and local finance in terms of the composition of the base of revenue sources and their yields. This article examines the effect of such changes on the potential future yield of consumption-based taxes. The effect of household characteristics and composition on the consumption of selected groups of goods subject to ad valorem retail sales taxes is estimated, generating demographic elasticities of consumption. These elasticities are applied to projected demographic changes in eight states through the year 2000. The results show rather wide variation in expected consumption shifts and potential tax bases across the states, with income growth having the greatest effect...." The geographical focus is on the United States.

Americas↗

Merkel cell carcinoma of the skin: imaging and clinical features in 93 cases.

Clinical, pathological and imaging data for 93 patients with Merkel cell carcinoma were reviewed. Median survival duration from the date of diagnosis was estimated using the Kaplan-Meier product-limit method. Survival durations of patients with no metastastic disease, with regional lymph node metastasis only and with distant metastases were compared using the Cox-Mantel log-rank test. The median age for patients with Merkel cell carcinoma was 70 years (range 35-91 years). The tumour occurred in 71 men and 22 women. The most common primary site was the head and neck region (64 patients), followed by the extremities (21 patients) and the trunk (10 patients). Median survival duration for the whole group was 33 months (range 2-140 months). Imaging studies of the primary sites were available for 10 patients and of metastatic sites for seven patients. Sonograms of the primary skin lesions showed single or multicentric hypoechoic nodules arising from the dermis and growing into the subcutaneous tissues. CT scans showed single or multiple minimally enhancing soft tissue nodules, in two instances associated with lytic bone erosion. The metastatic lesions were moderately hypoechoic on sonography and target-shaped with or without ring-enhancement on CT. Imaging studies have a limited role in diagnosis of the clinically evident primary skin lesions, but may be helpful in the assessment of the depth of the invasion and are crucial in the evaluation of regional and distant metastatic disease. If regional adenopathy is found then CT of the chest, abdomen and pelvis may be in order.

Adult↗

Development of new markers for hypoxic cells: [131I]Iodomisonidazole and [131I]Iodoerythronitroimidazole.

This study was aimed at developing ligands to evaluate tumor hypoxia by planar scintigraphy. Two 2-nitroimidazole analogues were developed as precursor compounds to image hypoxic tumors. Both tosylmisonidazole (Ts MISO) and tosylerythronitroimidazole (Ts ETNIM) were labeled with 131I. The biodistribution and autoradiographic evaluations by planar scintigraphy of 131I-IMISO and 131I-IETNIM were conducted at 1, 2 and 4 hours after administration to rats bearing 13762 breast tumors. Biodistribution of 131I-IMISO was also evaluated in Madison lung tumor-bearing mice. Intratumoral oxygen tension was measured by the Eppendorf system. Biodistribution showed similar tumor/blood and tumor/muscle count density ratios for both compounds. The thyroid uptake of both analogues was increased with time, suggesting in vivo deiodination probably occurred. Autoradiographs of 131I-IMISO and 131I-IETNIM revealed good visualization of the neoplasms. The tumor oxygen tension was 3-6 mmHg as compared to the normal tissue oxygenation of 30-40 mmHg. The findings indicate that these analogues can localize in the hypoxic region of solid tumors and may assist with quantitation of the hypoxic fraction of tumor for proper selection and evaluation of appropriate radiotherapy and chemotherapy.

Animals↗

Adenovirus masquerading as microsporidia.

Enterocytozoon bieneusi is a microsporidian that causes a severe, debilitating, chronic diarrhea in some patients with the acquired immunodeficiency syndrome. Specific diagnosis of E. bieneusi currently requires an invasive biopsy procedure and time-consuming preparation of specimens for electron microscopy. Our attempts to establish an in vitro culture system using mammalian cell cultures inoculated with duodenal aspirates, biopsy, or both, from 2 infected patients resulted in inadvertent coculture of an adenovirus and E. bieneusi. The adenovirus-infected cells deceptively appeared to contain spores of microsporidia based on light microscopic examination. Transmission electron microscopy revealed only a few microsporidia, but numerous cells infected with an adenovirus that was subsequently identified as adenovirus type 8. We believe that adenovirus infections prevented the cultured cells from supporting the proliferation of E. bieneusi and ultimately destroyed the cell cultures.

AIDS-Related Opportunistic Infections↗

Intraoperative lower extremity reflex muscle activity as an adjunct to conventional somatosensory-evoked potentials and descending neurogenic monitoring in idiopathic scoliosis.

STUDY DESIGN: Lower extremity polysynaptic reflexes and descending neurogenic motor and ascending somatosensory activity were recorded. OBJECTIVE: Two cases are presented to illustrate the intraoperative use of lower extremity reflex recordings for detecting compromise of spinal cord function. SUMMARY OF BACKGROUND DATA: Lower extremity reflex processing can be used to measure integrated spinal cord activity, whereas descending neurogenic and ascending somatosensory potentials measure only long tract function. METHODS: Eight channels of lower extremity polysynaptic reflex activity were recorded simultaneously after unilateral lower extremity mixed nerve stimulation. Sequential descending neurogenic and ascending somatosensory activity was recorded simultaneously with reflex recordings. RESULTS: In these two patients with idiopathic scoliosis, intraoperative reflexes changed before descending neurogenic and before ascending somatosensory activity changed. High-amplitude synchronous persistent reflex activity correlated with a postoperative neurologic deficit. Low-amplitude asynchronous transient reflex activity was not associated with a postoperative neurologic deficit. CONCLUSION: Intraoperative lower extremity reflex changes are more sensitive to spinal cord compromise than are changes in long tract function. Lower extremity polysynaptic reflexes monitor the integrated activity of the spinal cord that is responsible for the control of complex motor behavior.

Adolescent↗

Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases to the lungs from tumors implanted into the livers of rabbits.

BACKGROUND: This study evaluated the toxicity (Part I) and antitumor effects (Part II) associated with hepatic arterial infusion of recombinant platelet factor-4 (rPF4), an antiangiogenic protein. METHODS: Healthy rabbits (Part I) and rabbits with tumors implanted in their livers (Part II) received saline or rPF4 via hepatic arterial infusion. Three saline-receiving and four rPF4-receiving animals died 2-3 days postinfusion from gastroduodenal thromboembolism. The remaining animals were necropsied 3, 7, 10, or 14 days postinfusion. Blood analyses and hepatic angiography were performed before infusion and at the time of sacrifice. RESULTS: In Part I, focal coagulation necrosis of the hepatic parenchyma was observed in 1 of 11 rabbits that received saline and in 6 of 10 that received rPF4. In Part II, hepatic arterial infusion of rPF4 had no effect on growth of the implanted liver tumors. However, the protein significantly reduced the incidence of lung metastasis. CONCLUSIONS: Intraarterial infusion of rPF4 significantly reduced the incidence of lung metastasis. Nonheparin systemic anticoagulation may be needed during catheterization and infusion procedures to prevent thromboemboli.

Animals↗

Evaluation of intrapedicular screw position using intraoperative evoked electromyography.

STUDY DESIGN: This study analyzed the parameters needed for electrical stimulation of vertebral pedicle drill bits and screws. OBJECTIVES: The feasibility of using electrically evoked electromyography was studied. SUMMARY OF BACKGROUND DATA: Considerable potential for damage of adjacent nerve roots with incorrectly placed bits and screws exists with pedicular fixation of the lumbar spine. METHODS: Ninety-five drill bits, one hundred forty-four screws, and thirty-four exposed nerve roots were electrically stimulated in thirty-six patients. Simultaneous evoked electromyographic activity was recorded from four muscle groups in each lower extremity during partial neuromuscular blockade. RESULTS: A constant current threshold of 6 mA or less correlated with misplaced drill bits and screws that broached the cortex. Evoked electromyography was 93% sensitive whereas radiography was only 63% sensitive to detecting bits and screws that had broached the cortex. CONCLUSIONS: Evoked electromyography is a valuable sensitive adjunct to radiographic examination of pedicle drill bit and screw placement.

Adult↗

Gastrointestinal leiomyosarcoma metastatic to the liver. Durable tumor regression by hepatic chemoembolization infusion with cisplatin and vinblastine.

BACKGROUND: Gastrointestinal leiomyosarcoma metastatic to the liver is considered most resistant to any combination of systemic chemotherapy containing doxorubicin and/or ifosphamide. METHODS: Fourteen patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated with hepatic chemoembolization infusion consisting of polyvinyl alcohol sponge particles mixed with cisplatin powder (150 mg) followed by an intrahepatic arterial infusion of vinblastine (10 mg/m2). RESULTS: Ten major (> 50% regression) tumor responses were observed (70%) in patients lasting from 8 to 31+ months (median, 12 months) after an average of two hepatic chemoembolization procedures, usually 4 weeks apart. Transient side effects included right upper quadrant pain requiring narcotics, significant hepatic enzyme elevation, particularly of lactic dehydrogenase with a minimal increase in bilirubin, paralytic ileus requiring nasogastric suction up to 72 hours, urinary electrolyte losses (potassium+, magnesium++, sodium+) requiring supplements, and occasionally mild but transient leukopenia and thrombocytopenia. CONCLUSIONS: Hepatic chemoembolization infusion appears to induce a high rate of durable tumor response in patients with notoriously chemoresistant gastrointestinal leiomyosarcoma metastatic to the liver.

Adult↗

CEO summit. The leadership experience--roundtable discussion.

All across the country, hospitals, physicians and insurers are sizing each other up as potential strategic partners. But there's much ground to be covered before a final agreement is reached, and not every decision is based on facts and figures. Sometimes it's the personal interaction between CEOs that makes the deal happen--or not. McManis Associates and Hospitals & Health Networks brought together a roundtable of CEOs to talk about the ups and downs and the ins and outs of the leadership experience. Following is a series of first-person accounts by roundtable participants.

Chief Executive Officers, Hospital↗

Induction of heat labile alkaline phosphatase by butyrate in differentiating endometrial cells.

The addition of 2 mM sodium butyrate to monolayers enhances differentiation of Ishikawa endometrial cells. Cells from this cell line have been shown to enlarge and lift off the dish into dome structures over a period of 24-48 h in response to a factor in fetal bovine serum (FBS) [Fleming, 1995 J Cell Biochem in press]. When butyrate is added to monolayers, together with FBS, three- to fourfold higher numbers of differentiated structures, domes and predomes, can be counted. It had previously been shown [Holinka et al., 1986b] that estradiol induces heat stable placental alkaline phosphatase in Ishikawa cells. The addition of butyrate, on the other hand, results in a significant increase in levels of a heat labile alkaline phosphatase isozyme. The heat labile isozyme is also increased to some extent in cells stimulated to differentiate in response to FBS in the absence of butyrate. Differential inhibition by homoarginine and phenylalanine indicates that butyrate is inducing the liver-bone kidney isozyme that is found in endometrial glands in vivo.

Alkaline Phosphatase↗

Breastfeeding.

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Breast Feeding↗

In vitro culture and serologic and molecular identification of Septata intestinalis isolated from urine of a patient with AIDS.

Microsporidian spores were identified, on the basis of Weber's staining, in urine, stool, nasal, and saliva samples of an AIDS patient with diarrhea, hematuria, dysuria, and dementia. Urine and stool samples contained numerous spores, whereas few spores were seen in the nasal and saliva samples. Spores were concentrated from urine samples and inoculated into monkey kidney cell (E6) monolayers. After 6 to 8 weeks of culture, infected E6 cells filled with spores as well as spores free in the culture supernatants were seen daily. Transmission electron microscopy revealed that all stages of the parasite (CDC:V297) developed within septated, honeycomb-shaped parasitophorous vacuoles. Indirect immunofluorescence and immunoblotting studies using rabbit anti-Encephalitozoon cuniculi, anti-Encephalitozoon hellem, and anti-CDC:V297 sera revealed that CDC:V297 reacted intensely with the homologous serum but minimally with the heterologous sera. DNA isolated from CDC:V297, when PCR amplified with E. hellem and E. cuniculi primers, did not produce the diagnostic bands of approximately 547 and approximately 549 bp characteristic of E. hellem and E. cuniculi, respectively. On the basis of these studies, we concluded that CDC:V297 fits the description of Septata intestinalis (A. Cali, D. P. Kotler, and J. M. Orenstein, J. Eukaryot, Microbiol. 40:101-112, 1993).

AIDS-Related Opportunistic Infections↗