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Biomedical subjects

M Chang

Publications and source records attributed to M Chang.

211 records · Page 12Linked to original sources

A phase II clinical trial of the combination mitomycin C, adriamycin, and cis-diamminedichloroplatinum in patients with advanced upper aerodigestive cancer.

Twenty-seven patients with assessable, regionally advanced, or metastatic upper aerodigestive cancer of diverse histology received a combination of mitomycin C, adriamycin, and cis-diamminedichloroplatinum. All patients had previously received extensive surgery and/or radiation therapy. We observed an overall 46% partial response rate (12/26). This included seven of 15 (47%) responders with squamous cell carcinoma. Six of those seven patients responded within the initial month of treatment. For all study participants, the median time to progression and survival was 3.8 months and 7.3 months, respectively. Moderate-to-severe nausea, vomiting, anorexia, and alopecia were the most common toxicities. Myelosuppression (WBC less than 4,100 cells/mm3) and thrombocytopenia (PLTS less than 130,000 cells/mm3) occurred in 100% and 71% of the 21 patients with nadir data recorded, respectively. There were no episodes of sepsis nor did we detect any meaningful impairment in renal function. This regimen is active in the previously treated head and neck cancer patient and can be conveniently administered on an outpatient basis with acceptable and manageable side effects.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II clinical trial of the combination VP-16, bleomycin, and cis-diamminedichloroplatinum in patients with advanced upper aerodigestive squamous cell carcinoma.

Fifteen patients with advanced upper aerodigestive carcinomas of squamous cell histology received the three-agent cytotoxic regimen of VP-16, bleomycin, and cis-diamminedichloroplatinum (CDDP) administered as a continuous 120-h infusion. The objective response rate was 40%. Median times to progression and survival were 3.2 months and 4.3 months, respectively. Hematologic and gastrointestinal toxicities were relatively transient and manageable. Our experience indicates that this three-drug program does not offer a substantial therapeutic advantage compared with more conventional single agent cytotoxic approaches for advanced head and neck cancer.

Adult↗

A multicenter clinical trial of Gadolite Oral Suspension as a contrast agent for MRI.

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49-1.18 for reader 1: .46-1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.

Administration, Oral↗

Pharmacokinetics of a novel 5-lipoxygenase inhibitor (ABT-761) in pediatric patients with asthma.

OBJECTIVE: The pharmacokinetics of an N-hydroxyurea analog, ABT-761 in asthmatic pediatric patients with asthma were investigated. METHODS: A total of 24 patients were enrolled into this 8-day single- and multiple-dose study. Patients received daily doses of ABT-761 according to their body weight: patients of 20-38 kg received 50 mg; patients >38 kg but < or = 55 kg received 100 mg, and patients >55 kg received 150 mg. RESULTS: The mean values for the terminal phase t1/2 were 16-17 h after multiple-dose administration. When normalized for body weight, the mean day 8 Cl(f) values for 50-, 100-mg, and 150-mg doses were 0.57 (n=13), 0.51 (n=10), and 0.43 (n=1) ml x min(-1) x kg(-1), respectively, while the mean Vz/f values ranged from 0.75 to 0.77 l x kg(-1). The mean accumulation ratio observed (day 8 to day 1 AUC0-24 ratio) of ABT-761 was approximately 1.7, which is consistent with the t1/2 of this drug. Body weight, age, and body surface area were virtually identical in explaining the variability in dose-normalized Cmax and AUC values (R2=0.61-0.68). The percents of variance explained by these three variables were within a range of 3% for each pharmacokinetic parameter. CONCLUSIONS: The pharmacokinetics of ABT-761 in children were similar to those previously reported in adults. Body weight, age, or body surface area can be used to provide dosing adjustment for ABT-761 in pediatric patients.

Adolescent↗

Mouse and rat placental cell lines express abundant amounts of laminin.

Placental cell lines derived from midgestation placentae of outbred mice and rats were evaluated for the expression of the extracellular matrix protein laminin. The murine cell line, which has not been previously reported, demonstrates morphological characteristics similar to those of the rat cell line. Placental cell lines grow vigorously both in vitro and when transplanted to the peritoneum of allogeneic hosts. When transplanted, placental cells form cyst-like structures (with acellular cores) suspended in the peritoneal fluid, and invade abdominal structures forming solid masses. Using immunohistology, laminin was identified within in vitro cultured cells, within cyst-like structures and their acellular cores, and as a major component of the extracellular matrix of solid masses. Laminin was also identified in the normal rat chorioallantoic placenta. Evaluation of extracts from in vitro cultured placental cells, transplanted placental cells, and the normal chorioallantoic placenta by electrophoresis and immunoblotting demonstrated that laminins were composed of two species with molecular weights of 400,000 (A-chain) and 200,000 (B-chains). Mouse and rat placental cell lines may be valuable for studying laminin biosynthesis and function in the developing placenta.

Animals↗

Purification and sequencing of a rat intestinal 22 amino acid C-terminal CCK fragment.

Fractionation on Sephadex G50 gel of methanol extracts of rat intestine revealed two molecular forms of cholecystokinin (CCK) of about equal immunopotency: one form has an elution volume between CCK33 and CCK12; the other elutes in the salt region as does authentic CCK8. Purification and sequencing have demonstrated that the smaller molecular form is CCK8 with a sequence identical to the pork and sheep CCK8's that had previously been sequenced. Purification and sequencing of the larger molecular form reveals that it is a 22 amino acid C-terminal CCK fragment identical with pig CCK22 except that glycine instead of serine is present at the nineteenth residue from the C-terminus. This sequence is consistent with that predicted by cloned cDNA encoding preprocholecystokinin from a rat medullary thyroid carcinoma. CCK22 has not previously been reported to be a prominent molecular form in either pig or dog intestines.

Amino Acid Sequence↗

Unique cholecystokinin peptides isolated from guinea pig intestine.

Fractionation on Sephadex G50 gel of methanol extracts of guinea pig intestine reveals two molecular forms of cholecystokinin (CCK) of about equal abundance. One elutes at the position of CCK8 while the other elutes at a position intermediate between CCK33 and CCK8. Purification and sequencing of these peptides identify them as CCK8 and CCK22, respectively. Guinea pig CCK8 differs from other mammalian CCK octapeptides isolated thus far in that there is a valine substituted for methionine at position 6 from the C-terminus. In addition to the substitution in CCK8, serine is substituted for asparagine in position 22, glycine for serine in position 19, and asparagine for serine in position 15 from the C-terminus compared to the pig sequence. HPLC separation on a C18 column yields two peaks each of CCK8 and of CCK22 in pig intestinal tissue obtained from a commercial supplier. The two CCK8 peptides have identical amino acid sequences as do the two CCK22 peptides. The CCK22 peptides are equally bioactive in the guinea pig pancreatic acinar cell assay but are about 10-fold less potent than synthetic CCK8(s). One of the guinea pig CCK8 peptides is fully bioactive whereas the other is about 50-fold less potent compared to synthetic CCK8(s).

Amino Acid Sequence↗

A survey of Canadian hand therapists: demographics, roles, and educational needs.

A questionnaire was mailed to 236 occupational therapists (OTs) and physical therapists (PTs) practicing hand rehabilitation in Canada, to develop a demographic profile of practitioners, determine the scope of practice in Canada, and study educational and certification issues. The response rate was 78%, which provided an accurate profile. Sixty-two percent of respondents were OTs, 35% PTs, and 3% combined P/OTs. While 82% of respondents supported a certification process, only 13% were certified hand therapists. Forty-two percent practice with both OT and PT skills. Most respondents held bachelor's degrees and reported formal OT or PT education as their primary mode of acquiring knowledge. The high response rate indicated that commitment to and interest in the practice of hand therapy are strong in Canada. Therapists would like to see more continuing education offered in Canada, and a certification process to ensure professional standards.

Attitude of Health Personnel↗

Identity of tumour necrosis factor and the macrophage-secreted factor cachectin.

In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system. Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL). We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells). When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF). Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the 'cachectin' and 'TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.

Adipose Tissue↗

Esthetic outcome of implant-supported single-tooth replacements assessed by the patient and by prosthodontists.

PURPOSE: The objective of this study was to assess and compare patients' and clinicians' judgments of the esthetic outcome of implant-supported single-tooth replacements. MATERIALS AND METHODS: In all, 29 patients with 41 single implant-supported crowns in the maxillary anterior region participated in the study. The esthetic outcome of the implant-supported crowns was assessed by the patients and by 5 prosthodontists by means of a questionnaire in which various esthetics-related variables were addressed and responded to using visual analogue scales. Multiple regression analyses were used to evaluate the influence of the variables on the "overall satisfaction" with the implant-supported crown. RESULTS: Most variables in the patients' assessments revealed mean values above 90% and median values close to 100%. No single factor used in the multiple regression analysis was found to influence a patient's satisfaction with appearance of the crown at a statistically significant level. The clinicians' degree of satisfaction was for all variables lower than that of the patients. In 89% of the cases the clinicians could correctly locate the single implant-supported crown. Among the variables assessed, surrounding soft tissue appearance and form of the crown had the strongest influence on the clinician's overall satisfaction with the appearance of the crown. CONCLUSION: Appreciation of the esthetic outcome of the single implant-supported crowns was rated higher by the patients than by the prosthodontists. Furthermore, factors considered by professionals to be of significance for the esthetic result of the restorative treatment may not be of decisive importance for the patient's satisfaction.

Adolescent↗

Synovial excrescences and cysts of the spine: clinicopathological features and contributions to spinal stenosis.

Synovial cysts occur throughout the body and are generally benign lesions with limited clinical consequences. Juxtafacet cysts of the spine, in contrast, often press on a nerve root as it exits in the foramen, causing radiculopathy. Synovial tissue that emanates from the facet joint but extends medially, is an additional important cause of spinal stenosis. Over the past 5 years, neurosurgeons at our institution have operated on a large number of patients with back pain, with removal of abnormal synovial tissues. Histological examination of these tissues distinguishes the different types of pathologic processes responsible for producing symptoms. Juxtafacet cysts may be either mucin-filled ganglion cysts devoid of cyst lining or true synovial cysts with watery content and lined by synovial cells. Ganglion cysts arise in degenerated ligament at the facet joint, and occasionally within synovial stroma. Synovial cysts arise within synovium and, unlike synovial cysts in the extremities, have a thick wall containing granulation tissue, numerous histiocytes and giant cells. This hyperplastic, irritated synovium of the spine, which we term "synovial excrescences", is voluminous and this reactive part overshadows the cystic portion of the lesion in most instances. Iron pigment deposition and inflammation are mild to absent, making synovial excrescences different from pigmented villonodular synovitis. Synovial excrescences of the spine are an important cause of spinal stenosis, predominantly in elderly patients. Surgical removal of excrescences protruding into the spinal canal provides prompt and durable relief of symptoms, usually without the need for extensive bony laminectomy or spinal fusion. Several patients in our study had both spinal ganglion cysts and synovial excrescences, suggesting common risk factors for both lesions.

Aged↗

MR body stereotaxis: an aid for MR-guided biopsies.

The use of a new body stereotactic system to facilitate magnetic resonance (MR) guided biopsies is described. A skin entry point is first found using a localizer MR scan. The articulating arm of the stereotactic unit is then used to aim the MR needle at the entry point and accurately maintain the needle at the correct angle to intersect the target area. Complex angles may be used to allow needle passes outside the scan plane. This is accomplished by angling the arm out of the plane of the section.

Biopsy↗