Integument flaps incorporating the nutrifying arteries of cutaneous nerves and/or cutaneous veins.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
S M Chang
Publications and source records attributed to S M Chang.
Phase II study of phenylacetate in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.
PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.
Adult↗
Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.
PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
Adult↗
The role of paclitaxel in the treatment of primary and metastatic brain tumors.
The rationale for the use of paclitaxel to treat brain tumors includes impressive activity in a wide array of chemotherapy-resistant solid tumors, in vitro and in vivo evidence of cytotoxicity against primary brain tumors, and a paucity of effective alternative agents. A review of published studies evaluating paclitaxel alone or in combination with other chemotherapeutic agents suggests that paclitaxel alone is not highly active against newly diagnosed or recurrent glioblastoma multiforme. However, additional prospective trials are warranted to evaluate the efficacy of paclitaxel plus conventional cranial irradiation or stereotactic radiosurgery. Single-agent paclitaxel appears to be active against gliomas with an oligodendroglial component and may prove useful both as a component of initial therapy and for recurrent disease. Activity against anaplastic gliomas and brain metastases also should be explored. With radiation, a weekly paclitaxel administration schedule is particularly appealing from pharmacologic, safety, and dose-intensity perspectives. In addition, the dose of paclitaxel must be increased in patients who are concurrently receiving medications that induce the P-450 drug metabolizing system. Primary and metastatic brain tumors constitute a very difficult problem in oncology. Future investigations should be directed at evaluating paclitaxel-based chemotherapy regimens in selected brain tumor types, combining paclitaxel with stereotactic radiosurgery, and determining the importance of other proposed mechanisms of action of paclitaxel (eg, inhibition of angiogenesis and tumor invasion).
Antineoplastic Agents, Phytogenic↗
Term pregnancy in a noncommunicating rudimentary horn of an unicornuate uterus: a case report.
A case of full-term pregnancy in the noncommunicating rudimentary horn of unicornuate uterus is presented. A healthy female infant weighing 2,985 g was delivered by cesarean section at 37 weeks' gestation. The diagnosis was missed by prenatal ultrasonography and was made only at laparotomy. A retrospective analysis of our ultrasound studies revealed that the echo pattern of the nongravid uterus resembled a soft pelvic mass. Color Doppler imaging revealed prominent low-impedance uterine arcuate-radial arterial blood flow surrounding the periphery of the pelvic mass, as well as multiple areas of placental implantation with a pulsatile lacunar flow pattern. A high index of suspicion of rudimentary horn pregnancy should be borne in mind whenever late-pregnancy ultrasonography shows the above-mentioned characteristic ultrasonic findings.
Adult↗
The nutritional status of rural Jamaican school children.
Three thousand, eight hundred and eighty-two (3,882) children in grades 2-5, attending 16 rural primary and all-age schools in central Jamaica were weighed and their weight-for-age standard deviation scores calculated using the World Health Organization/National Center for Health Statistics (WHO/NCHS) references. Heights were also measured in a random sample of the grade 5 children (n = 793) and height-for-age and body mass index (BMI-kg/m2) calculated. Sixty-nine per cent of the total sample were of normal weight-for-age, 2% were moderately undernourished (weight-for-age > -3 Z-score, < or = -2 Z-score), and a further 24% mildly undernourished (weight-for-age > -2 Z-score, < or = -1 Z-score). Few children were overweight. The frequency distribution of weight-for-age was similar in girls and boys. In the subsample of children in whom heights were measured, 25.8% were < or = -1 Z-score height-for-age, and of these 4.9% were < -2 Z-score. Compared with a survey conducted in a similar rural area in the 1960s, the children's mean weights for age group categories were 1.1 to 3.7 kg heavier. Children who were older than appropriate for their grade were more likely to be undernourished (Odds ratio 3.94, 95% CI 3.21, 4.83), which suggests that undernourished children may be more likely to repeat a grade or start school later.
Body Constitution↗
Possible existence of quaternary structure in the high-affinity serotonin transport complex.
Deletion-mutants of the cloned mouse serotonin transporter (SERT) rendered dominant negative-mutant effects upon wild-type transporter activities in heterologous expression studies; such effects were transporter-selective and did not influence the activities of co-expressed neuronal GABA transporter. Heterologous expression of linear concatenates (up to four copies) of SERT further revealed discernable uptake activities for both transporter-dimer and -tetramer, but not for the trimer. Kinetic and pharmacological analyses revealed that the monomer, dimer, and tetramer manifested comparable transport Km and potencies for known serotonin uptake inhibitors; the tetramer was distinct from the others only in manifesting notably reduced transport Vmax. Surprisingly, equivalent cocaine congener-binding activities were observed for all concatenates, including the functionally inactive trimer. These findings collectively support the existence of quaternary structure in the active 5-HT transport complex; such structure is likely to be a critical determinant of ligand transport activities, but apparently not of transporter-inhibitor interactions.
Animals↗
Genetic immunization of chimpanzees chronically infected with the hepatitis B virus, using a recombinant retroviral vector encoding the hepatitis B virus core antigen.
Cytotoxic T lymphocyte (CTL) activity and CD4+ helper T cell responses to the hepatitis B virus (HBV) core antigen (HBcAg) have been implicated in clearance of acute and chronic HBV infections. We showed that intramuscular injections of a novel recombinant retroviral vector expressing an HBcAg-neomycin phosphotransferase II (HBc-NEO) fusion protein induces HBc/eAg-specific antibodies and CD4+ and CD8+ T cell responses in mice and rhesus monkeys. We have now immunized three chronically infected chimpanzees, each with 10(10) CFU of nonreplicating retroviral vector particles expressing the HBc-NEO fusion protein. Of two immunized chimpanzees examined for CTL responses, one developed HBcAg-specific CTLs and showed marginal, transient elevations of alanine aminotransferase (ALT) levels following injection. However, both chimpanzees remained positive for serum HBeAg, negative for anti-HBe antibody by conventional assays, and displayed no change in HBV viral load throughout the study. In contrast, the third chimpanzee exhibited a traditional seroconversion evidenced by a loss of serum HBeAg and the subsequent emergence of anti-HBe antibodies within 24 weeks after the first injection. Simultaneously, two transient ALT flares and a significant decrease in the serum HBV DNA levels were noted. Despite its limitations, the present study demonstrates (1) the safety of treatment with high titers of retroviral vector in chimpanzees, (2) the capability of a retroviral vector expressing HBcAg to stimulate immune responses in HBV chronic carrier chimpanzees, and (3) that retroviral vector immunization may be therapeutically beneficial in the treatment of chronic HBV infection.
Amino Acid Sequence↗
Radiation therapy and hydroxyurea followed by the combination of 6-thioguanine and BCNU for the treatment of primary malignant brain tumors.
PURPOSE: This study was designed to evaluate a combined modality treatment for malignant gliomas using radiation therapy with a radiosensitizer and an adjuvant chemotherapy regimen designed to modify resistance to BNCU. METHODS AND MATERIALS: Patients were eligible if they were 15 years of age or older, and had newly diagnosed glioblastoma multiforme (GBM), or anaplastic glioma (AG). Treatment consisted of external beam radiotherapy given to a dose of 60 Gy using a single daily fraction Monday to Friday. Concurrent hydroxyurea at a dose of 300 mg/m2 every 6 h every other day was given during radiation. Following radiotherapy, patients were then treated with BCNU and 6-Thioguanine (6TG). The 6-TG was given by mouth every 6 h for 12 doses prior to BCNU. Patients were initially treated with 60 mg/m2/dose of 6TG, with escalation to a maximum dose of 100 mg/m2/dose. The primary study end points were time to tumor progression and survival. RESULTS: A total of 245 eligible patients were enrolled from 1/18/88 to 12/26/91. The histologic subtypes included 135 GBM, and 110 with AG (103 with anaplastic astrocytoma, 7 with high-grade mixed oligoastrocytoma). For the GBM group, the median time to tumor progression (TTP) and median survival were 33 (95% CI 26, 39) and 56 (95% CI 49, 69) weeks, respectively. For the AG group the median TTP was 282 weeks (95% lower confidence bound = 155 weeks). Median survival for this group has not been reached (95% lower confidence bound = 284 weeks) with a median follow-up for surviving patients of 298 weeks. A proportional hazards model was used to look at potential prognostic factors for survival, including initial Karnofsky Performance Scale (KPS), age, and extent of surgery, as well as dose of 6TG. Higher KPS, and lower age, predicted for longer survival (p < 0.01, < 0.001) in GBM patients; lower age was significant (p = 0.05) for AG cases. A higher (greater than 95 mg/m2) or lower dose of 6TG was not statistically significant in this model. CONCLUSIONS: This therapy was no more effective in patients with GBM than other reported series. In patients with malignant gliomas other than GBM, prolonged progression-free and overall survival is noted, without a median survival reached at the time of this report. In this subset of AG patients, survival is comparable to recent studies using halogenated prymidines during radiation and Procarbazine, CCNU, and Vincristine (PCV) as adjuvant chemotherapy.
Adolescent↗
High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma.
Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. Interferon-alpha [6 x 10(6) U subcutaneously three times per week] and tamoxifen (240 mg/m2/day orally) were administered continuously. Treatment response was assessed at 6 week intervals using clinical and radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. Median age was 41 years (range 23-61 years). All patients had gliomas that progressed after radiation therapy and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible moderate to severe neurological toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses of 240 mg/m2/day. Although the initial tamoxifen dose was reduced to 120 mg/m2/day, moderate neurotoxicity was noted at this dose as well and the trial was closed early. The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure. Of 16 evaluable patients, 12 had progressive disease after one cycle of treatment, 3 had stable disease, and there was one minor response. Gradual dose escalation may be required if similar patients are to be treated with high dose tamoxifen in conjunction with interferon.
Administration, Oral↗
Schoolchildren's diets and participation in school feeding programmes in Jamaica.
OBJECTIVES: To describe food consumption during the school day of rural Jamaican children and participation in two government school feeding programmes. To determine factors which were related to these. DESIGN: Cross sectional. SETTING: 16 primary schools in rural Jamaica. SUBJECTS: 415 children in grades 2 and 5 (ages 7 and 10 years). RESULTS: Consumption of sweets, sweet drinks and snacks was high. Mean intakes at lunch were: energy 1537 kJ (SD 756), protein 10.4 g (SD 7.6) and iron 1.5 mg (SD 1.2). The mean energy intake was 17-20% of the daily requirement for this age group. Two types of school feeding programmes were available in the schools, one provided a cooked meal and the other a bun and milk. Median availability of school meals (as a percentage of children enrolled in the schools) over three terms was 24.6% (range 0-85.4%). Twenty per cent of the children participated in one or other programme. Poorer children were more likely to participate in the bun and milk programme (odds ratio 2.1, 95% CI 1.3-3.5) but children with more money to purchase food participated in the more costly cooked meal programme (odds ratio 2.4, 95% CI 1.3-4.6). CONCLUSIONS: Energy intakes at lunch in Jamaican children were somewhat below optimal levels and the reliance on sweets and snacks is an area of concern. Programme characteristics such as meal cost, may affect access to school feeding by poor children.
Analysis of Variance↗
Undernutrition and elevated blood lead levels: effects on psychomotor development among Jamaican children.
OBJECTIVE: We examined whether or not the effect of elevated blood lead levels on children's psychomotor development was modified by their nutritional status. DESIGN: Anthropometry, developmental quotients (DQs), blood lead levels and haemoglobin were measured in lead exposed and unexposed children with different levels of nutritional status. Social background and maternal height and verbal intelligence were also measured. Testers, anthropometrists and interviewers established reliabilities with a trainer before the study began. SETTING: Children were from two suburban areas in Kingston, Jamaica. All measurements on the children were carried out at a research unit. Social background and maternal measurements were carried out at the children's homes. SUBJECTS: The exposed group comprised 58 children (3-6 years) attending the same preschool which was situated in a lead contaminated environment. The unexposed group comprised 53 children attending a nearby preschool without lead contamination. RESULTS: The exposed children had significantly higher blood lead levels and lower DQs, and their homes had poorer facilities than the unexposed children. The deficit in DQ was greater (10.6 points) among children with weight for height less than -1 SD (National Center for Health Statistics references) than among better nourished children (2 points). CONCLUSIONS: Undernourished children exposed to lead may have more serious developmental deficits than better nourished children.
Child↗
Nutrition and education: a randomized trial of the effects of breakfast in rural primary school children.
Hunger during school may prevent children in developing countries from benefiting from education. Although many countries have implemented school feeding programs, few programs have been rigorously evaluated. We conducted a randomized, controlled trial of giving breakfast to undernourished and adequately nourished children. The undernourished group comprised 407 children in grades 2-5 in 16 rural Jamaican schools (weights-for-age < or = -1 SD of the National Center for Health Statistics references) and the adequately nourished group comprised 407 children matched for school and class (weights-for-age >-1 SD). Both groups were stratified by class and school, then randomly assigned to breakfast or control groups. After the initial measurements, breakfast was provided every school day for 1 school year. Children in the control group were given one-quarter of an orange and the same amount of attention as children in the breakfast group. All children had their heights and weights measured and were given the Wide Range Achievement Test before and after the intervention. School attendance was taken from the schools' registers. Compared with the control group, height, weight, and attendance improved significantly in the breakfast group. Both groups made poor progress in Wide Range Achievement Test scores. Younger children in the breakfast group improved in arithmetic. There was no effect of nutritional group on the response to breakfast. In conclusion, the provision of a school breakfast produced small benefits in children's nutritional status, school attendance, and achievement. Greater improvements may occur in more undernourished populations; however, the massive problem of poor achievement levels requires integrated programs including health and educational inputs as well as school meals.
Absenteeism↗
Survival and functional status after resection of recurrent glioblastoma multiforme.
OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution.
Adolescent↗
Chain-linked directional vascular plexuses of the integument and link-pattern vascularized flaps in distal extremities.
Explore the source record for details and available documents.
Extremities↗
DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector.
Previously we reported the development of a plasmid DNA expression vector system derived from Sindbis virus (T. W. Dubensky, Jr., et al., J. Virol. 70:508-519, 1996). In vitro, such vectors exhibit high-level heterologous gene expression via self-amplifying cytoplasmic RNA replication. In the present study, we demonstrated the in vivo efficacy of the Sindbis virus-based pSIN vectors as DNA vaccines. A single intramuscular immunization of BALB/c mice with pSIN vectors expressing the glycoprotein B of herpes simplex virus type 1 induced a broad spectrum of immune responses, including virus-specific antibodies, cytotoxic T cells, and protection from lethal virus challenge in two different murine models. In addition, dosing studies demonstrated that the pSIN vectors were superior to a conventional plasmid DNA vector in the induction of all immune parameters tested. In general, 100- to 1,000-fold-lower doses of pSIN were needed to induce the same level of responsiveness as that achieved with the conventional plasmid DNA vector. In some instances, significant immune responses were induced with a single dose of pSIN as low as 10 ng/mouse. These results indicate the potential usefulness of alphavirus-based vectors for DNA immunization in general and more specifically as a herpes simplex virus vaccine.
Animals↗
Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.
PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel administered as a 3-hour infusion in patients with recurrent malignant glioma. PATIENTS AND METHODS: Patients were stratified by starting dose of paclitaxel and concurrent anticonvulsant (AC) use and were treated in cohorts of three patients. The starting dose was 240 mg/m2 administered intravenously with escalations of 30 mg/m2 until the MTD was established. Pharmacokinetic data were obtained for each patient for the first infusion. Tumor response was assessed at 6-week intervals and treatment was continued until documented tumor progression, unacceptable toxicity, or a total of 12 paclitaxel infusions. RESULTS: From April 1995 to December 1996, 34 patients were treated; 27 patients in the AC group and seven patients in the non-AC group. The MTD for patients who received ACs was established at 360 mg/m2 and the dose-limiting toxicity (DLT) was central neurotoxicity, characterized as transient encephalopathy and seizures. In contrast, the MTD for patients who did not receive ACs was 240 mg/m2, and myelosuppression, gastrointestinal toxicity, and fatigue were the DLTs. Pharmacokinetic data confirmed that the plasma drug levels and clearance rates were similar for patients in both groups at the respective dose levels that produced DLTs. CONCLUSION: The pharmacokinetics of paclitaxel are altered by ACs, and significantly larger doses of the drug can be administered to patients with brain tumors on AC therapy. The toxicity profile is different for patients on AC therapy treated at these higher doses. A phase II study has been initiated that uses a dose of 330 mg/m2 for patients on AC therapy and 210 mg/m2 for patients not on AC therapy.
Adult↗
Concomitant and hormonally regulated expression of trp genes in bovine aortic endothelial cells.
Recent findings have suggested that the vertebrate trp family of channel proteins is the structural basis for Ca2+ influx through the capacitative calcium entry (CCE) pathway. We have discerned, in bovine aortic endothelial cells, the concomitant expression of four such vertebrate genes: trp-1 (two splice variants), trp-3, trp-4 and trp-5. Exogenous hormones rendered dynamic effects on the transcript levels of these genes. Most notably, beta-estradiol significantly down-regulated trp-4 while trans-retinoic acid dramatically up-regulated trp-5; yet these hormones rendered little change in CCE. These findings suggest that the extent of a given trp channel's participation in CCE is not reflected in alterations of its transcript level.
Amino Acid Sequence↗