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Biomedical subjects

A H Shikani

Publications and source records attributed to A H Shikani.

18 recordsLinked to original sources

Beta-1 integrin expression by human nasal chondrocytes in microcarrier spinner culture.

Beta-1 integrin plays a major role in cell attachment and is believed to be involved in mediating the interactions of chondrocytes with their environment. We previously reported that articular chondrocytes propagated in microcarrier spinner culture proliferated and reexpressed their chondrocytic protein. The goal of the present study was to investigate the expression of beta-1 integrin by chondrocytes growing on the surface of microcarriers. Nasal chondrocytes (4 x 10(3)/cm(2)) were seeded on microcarriers and incubated at 37 degrees C, 5% CO(2), 60 rpm. Expression of chondrocyte markers and beta-1 integrin was determined using reverse transcriptase-polymerase chain reaction and immunocytochemical analyses. De novo synthesis of sulfate-containing proteoglycans was studied using 35SO(4) incorporation techniques. Like articular chondrocytes propagated in microcarrier spinner culture, nasal chondrocytes expressed high levels of collagen type II mRNA, whereas collagen type I mRNA levels were low. Aggrecan mRNA was detectable and levels of de novo 35SO(4) incorporation were high. Chondrocytes immunostained intensely for collagen type II and keratan sulfate but did not stain for collagen type I. beta-1 integrin mRNA levels were high, and the protein was immunolocalized to regions of cell-to-cell or cell-to-microcarrier contact. The fact the chondrocytes expressed high levels of beta-1 integrin raises the possibility that this integrin molecule has a role in the maintenance of the chondrocytic phenotype.

Aggrecans↗

Polymer chemotherapy for head and neck cancer.

OBJECTIVES: To study a new method of delivery of chemotherapy for the treatment of squamous cell carcinomas (SCCs) of the head and neck, to evaluate the pharmacokinetics of four anticancer agents (cisplatin, fluorouracil [5-FU], methotrexate [MTX], and paclitaxel) loaded into the biodegradable polymer, polyanhydride polymer poly(FAD:SA), and to evaluate the effectiveness and toxicity of the drug-polymer combination against human SCCs, both in vitro and in vivo. STUDY DESIGN: Poly(FAD:SA) was loaded with different chemotherapeutic drugs and its in vitro and in vivo drug release and tissue penetration characteristics were studied. The biocompatibility and toxicity of the polymer-drug combination were determined. The effectiveness of the drug-polymer was evaluated against three different human SCCs (larynx O11, pharynx FADU, and floor of mouth UM- SCC1) cultured in vitro and in nude mice carrying human SCC xenografts. METHODS: The in vitro drug release pharmacokinetics of the drugs were performed using atomic absorption spectrometry for cisplatin and high-pressure liquid chromatography for the 5-FU, MTX, and paclitaxel studies. In vitro tumor cytotoxicity was assessed by growth assay. In vivo cytotoxicity was assessed by growth rate inhibition in a nude mouse model. RESULTS: All four chemotherapy drugs demonstrated a continuous release that followed first-order kinetics from the polymer. More than 95% of the MTX and 5-FU, 70% of the cisplatin, and 20% of the paclitaxel was released within the 10 days of the assay. Tumor cytotoxicity revealed that the polymer was very effective against the human SCCs O11, FADU, and UM- SCC1 in vitro. When a small amount of polymer (1-2 g) was added to the cell culture and left for 7 days, 96.6% of the UM-SCC1 cells, 86.9% of the FADU cells, and 94.6% of the O11 cells were killed. When the culture medium was then changed every 2 days to remove the effect of nutrient depletion or chemicals released by the degrading polymer, 74% of the UM-SCC1 cells, 94.5% of the FADU cells, and 66.1% of the O11 cells were killed at 7 days. The tumor animal model was the nude mouse carrying human floor of mouth SCC xenografts. Different amounts of cisplatin were incorporated into the polymers (5% and 7% drug/polymer at a weight/weight [wt/wt] load). Thirty-five days after implantation of the polymer in nude mice, the mean treated tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation the mean treated tumor size was 41.4% of controls in the 5% group and 38.1% in the 7% group, indicating a statistically significant delay of tumor growth compared with controls or with intraperitoneally injected cisplatin. The blank polymer was well tolerated by the mouse and had no effect on tumor growth. CONCLUSIONS: The study results indicate that polymer chemotherapy is effective against a variety of SCCs of the head and neck, both in vitro and in vivo, and may become a useful therapeutic option for head and neck cancer.

Animals↗

Polymer-iodine inactivation of the human immunodeficiency virus.

BACKGROUND: Hospital and laboratory equipment that come in contact with body fluids of patients with human immunodeficiency virus (HIV) are potentially infective and require special measures for decontamination and disposal. Human immunodeficiency virus is sensitive to several chemicals but requires a continuous exposure to the disinfectant to effective inactivation. Polymers have the capacity to release viricidal chemicals in a sustained fashion for prolonged periods of time, and may be used to coat patient care items before their use. Iodine was chosen because of its universal antimicrobial potential; it was incorporated into polyurethane polymers and the effectiveness of the polymer-iodine against HIV-1 3B was assayed. STUDY DESIGN: Iodine was loaded into polyurethane polymers by two different methods: polyurethane-complexing, where the iodine is released through a desorption mechanism, and polyurethane-matrixing, where the iodine is released through a diffusion mechanism. The pharmacokinetics of the iodine release were studied in each case. Twenty-four-well viral culture plates used for HIV-1 3B assays were coated with both types of polyurethane-iodine polymers. Their effectiveness against HIV was assessed by MT4 cell viability and reverse transcriptase assays. RESULTS: The polymer-iodine combination remained stable as long as it was dry: the iodine release started only when the plates came in contact with an aqueous environment. The release from the polyurethane-iodine complex was large and rapid, resulting in inactivation of the HIV-1 3B within 15 to 30 minutes, as determined both by reverse transcriptase and the MT4 cytopathic cell cultures assays. The release from the polyurethane-iodine matrix was slower and had no significant antiviral effect. CONCLUSIONS: The polyurethane polymer provided a sustained release of iodine that effectively inactivated HIV. The coating may be applied at the time of manufacturing to specific hospital and laboratory items that are to come in contact with blood from patient-contaminated fluids. This technology is attractive for decontamination, especially in situations where appropriate and rapid disposal of medical waste is not readily available. Further research is in progress to speed the release of the iodine from the polymer and the subsequent inactivation of the virus.

Delayed-Action Preparations↗

Expandacell, a new sponge for endoscopic sinus surgery.

Hydroxylated polyvinyl acetal (PVAc) sponges are routinely used for control of bleeding following endoscopic sinus surgery. The physical characteristics of the Meroce sponges and the new Expandacell sponges were evaluated, including pore diameter, sponge size and rate of expansion. The Expandacell sponges were found to have a smaller pore diameter and to expand more slowly, giving the surgeon a bit more time for placement of the pack in the middle meatal cavity. Changing the physical characteristics of the PVAc sponges, such as making the pore size smaller, decreasing the thickness, coating with a laminated polyethylene surface or placing a fenestration in the center of the sponge, resulted in a significant decrease in the degree of pain associated with removal of the sponge.

Animals↗

Use of antibiotics for expansion of the Merocel packing following endoscopic sinus surgery.

Sinus packs that are used for hemostasis and the prevention of synechiae following endoscopic sinus surgery frequently get colonized with bacteria from the infected sinus, which increases the risk for infection. This study was conducted in an attempt to characterize the bacterial flora of the chronically infected sinus, and to evaluate whether direct installation of antibiotics into the sponge inhibits bacterial growth. Bacteria were cultured from 89% of the sinuses at surgery, and in 67% of the cases, the same bacteria were recovered from the sinus dressings one week later. When the Merocel sinus dressing was expanded with a combination of polymyxin, neomycin and hydrocortisone at the time of surgery, a 36% decrease in bacterial growth was observed, along with a decrease in the severity of pain associated with removal of the pack. This supports the concept of using an antibiotic for the expansion of the sponge following endoscopic sinus surgery.

Adolescent↗

Polymer delivery of chemotherapy for squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy for the treatment of squamous cell carcinoma of the head and neck is limited by the systemic toxicity of chemotherapeutic agents. An attractive alternative is the controlled and sustained release of anticancer agents from a resorbable polymer delivery system that is implanted next to the tumor. The advantages are a high locoregional drug concentration with low systemic levels and a delivery system that is not limited by poor blood supply caused by previous radiation therapy or surgery. METHODS/SUBJECTS: The polymer used in this study was a biodegradable polyanhydride made up of fatty acid dimer and sebacic acid, Poly (FAD-SA), loaded with cisplatin. The tumor animal model was the nude mouse carrying human floor of mouth squamous cell carcinoma xenografts. Polymer-cisplatin pharmacokinetics and the effect of polymer delivery of cisplatin (5% and 7% drug/polymer at a weight/weight load) on tumor growth rates were evaluated. MAIN RESULT: Thirty-five days after implantation of the polymer, the mean treated tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation, the mean treated tumor size was 41.4% of controls in the 5% group and 38.1% in the 7% group, indicating a statistically significant delay of tumor growth compared with controls or with intraperitoneally injected cisplatin. CONCLUSION: This study demonstrates that continuous release of cisplatin directly at the tumor site, using an implantable polymer, is effective against human head and neck squamous cell carcinoma xenografts in nude mice.

Animals↗

Juvenile nasopharyngeal angiofibroma tumor models. Failure of androgens to stimulate growth in nude mice and in vitro.

Juvenile nasopharyngeal angiofibroma is a tumor with a predilection for adolescent boys. It has been shown to contain cytosolic androgen receptors and to regress with estrogen therapy; however, the results have not been consistent. Extensive investigation has been unable to settle this issue in patients owing, in part, to the rarity of these tumors. We have attempted to establish a tumor model for juvenile nasopharyngeal angiofibroma by transplanting the tumor into the subdermal space of athymic mice and also by culturing it in vitro, to study the effect of hormonal manipulation. The tumor did survive in male and female athymic mice but has failed to grow. Androgen treatment of the mice of either sex did not alter its survival or growth behavior. The in vitro tissue culture grew fibroblastoid cells that were not stimulated by androgen supplementation. This study suggests that factors other than androgens are at least complementary, if not essential, in promoting the growth of juvenile nasopharyngeal angiofibroma in tumor models, and that androgens are not, in and of themselves, sufficient growth stimuli.

Animals↗

Radiolabeled antibody therapy for squamous cell carcinoma of the head and neck.

Immunohistochemical staining for ferritin was performed on 11 human head and neck squamous cell carcinomas transplanted in nude mouse xenografts. Seven tumors were found to be positive. Using ferritin as a tumor antigen target, escalating doses of yttrium-90-labeled antiferritin antibodies were injected intravascularly into nude mice that were transplanted with a ferritin-positive human squamous cell carcinoma. Forty-five days after injection, the mean treated tumor size was 25.6% of control in the 100-microCi group, and 20.6% of control in the 200-microCi group. Ninety days after injection the mean tumor size was 27.5% that of control in the 100-microCi group and 31.7% in the 200-microCi group. Higher doses of radiation (300 and 400 microCi per mouse) caused death of most of the animals due to radiation toxicity. Presensitization of the animal, before antibody injection, with a bolus intraperitoneal injection of 7.5 mg of cisplatin per kilogram of body weight, resulted in further reduction in tumor size when compared with antibody alone or cisplatin alone. This study demonstrates that radioimmunotherapy with selected doses of yttrium-90-labeled antiferritin antibodies is effective against human head and neck squamous cell carcinoma xenografts in nude mice.

Animals↗

Irreversible unilateral visual loss due to acute sinusitis.

Extension of sphenoethmoiditis into the orbital apex may result in visual loss and ophthalmoplegia, but minimal signs of orbital pathology such as proptosis, chemosis, or lid edema. This entity is termed orbital apex syndrome. The case of a 74-year-old woman with orbital apex syndrome and irreversible unilateral visual loss secondary to bacterial sphenoethmoiditis is presented. This case, and our review of the literature, suggest that patients with symptomatic acute sphenoethmoiditis are at a relatively higher risk of permanent visual loss than those with sinusitis not involving the posterior ethmoid and/or sphenoid sinuses.

Acute Disease↗

Effect of viruses and interferon on chick embryo otocyst cultures.

Chick embryo otocyst organ cultures were subjected to live vesicular stomatitis virus and rubella virus preparations, to interferon (IFN), and to a combination of both virus and IFN, and compared to control untreated otocysts. We observed morphologic and microscopic changes suggestive of individual cell death and delayed organ differentiation in the virus-treated groups, along with an appreciable decrease in size of the otocyst. Low-dose IFN treatment prior to virus inoculation appeared to partially prevent these effects. The addition of IFN alone did not seem to affect the differentiation process. Time-lapse videophotography further confirmed the above findings. This study suggests that the peripheral component of congenital deafness associated with viral infections is likely to be an effect of the virus itself, and not of the IFN. Interferon provides a partial protective effect against the insult from the virus in vitro and does not seem to be toxic to the developing otocyst.

Animals↗

Salmonella neck abscess.

Salmonella species represent uncommon causative agents in focal infections of the head and neck. The case of a 24-year-old diabetic man with a neck abscess caused by Salmonella enteritidis is presented, and the relevant literature is reviewed. Salmonella should be included in the differential diagnosis of head and neck abscesses.

Abscess↗