Biomedical subjects
Publications and source records attributed to L Hui.
The use of dexamethasone in the management of bacterial meningitis in adults remains controversial. This report illustrates the case of a 27-year-old male with severe meningococcal meningitis and meningococcemia who completely recovered after receiving antibiotics and dexamethasone. In adults with suspected bacterial meningitis, especially in high risk cases, the adjunctive use of dexamethasone may be beneficial.
Emphysematous pyelonephritis is a rare, severe, necrotizing form of renal infection characterized by the presence of gas within the renal parenchyma or perinephric space. In patients suspected of emphysematous pyelonephritis, computed tomography scan should be done promptly. Based on the available data and this case, surgical intervention appears to be the preferred treatment.
Twenty-five patients with metastatic breast cancer were treated with ICE after failure of previous chemotherapy. Their median age was 50 years (range 36-73). All but 1 patient had multiple sites of metastases. Nineteen (76%) patients had undergone two or more chemotherapy regimens for metastatic disease prior to ICE. The performance status (PS) of the patients was Eastern Cooperative Oncology Group (ECOG) 0:6; 1:12; 2:5; 3:2. Ifosfamide 1.25 g/m(2) over 3 h D1-3 along with mesna, etoposide 80 mg/m(2) D1-3 and carboplatin 300 mg/m(2) D1 were given every 3 weeks. We observed a partial response in 10 patients (40%, 95% confidence interval 21-62%). The response duration ranged from 1 to 15 months with a median duration of 4.5 months. The survival of all 25 patients ranged from 10 days to 25 months, with a median of 9 months. All 25 patients were evaluable for toxicity. Thirteen patients (52%) experienced grade 4 hematological toxicity, which improved after growth factor support. Four patients had leukopenic fever, 1 had gram-negative sepsis, while 2 had Clostridium difficile enterocolitis and another had herpes zoster reactivation. Four patients (16%) experienced grade 3-4 gastrointestinal (G-I) toxicity. No hepatic or renal toxicity was observed (1 patient had microscopic hematuria). One patient died of G-I bleed, and another patient died at home of undetermined cause. We conclude that ICE is an effective salvage regimen in metastatic and refractory breast cancer, even in heavily pretreated patients, and is a tolerable treatment when used with growth factor.
One hundred thirty-eight patients with Duchenne/Becker muscular dystrophy (DMD/BMD) were screened with complete cDNA probes and the multiplex polymerase chain reaction (mPCR) amplification of 18 pairs of oligonucleotide primers. Eighty-six deletions and 4 duplications were detected, the deletion frequency being 62.3%. Eighty-two deletions were detected with the two sets of primers described by Chamberlain et al. and Beggs et al, which was 95.4% of deletions detected by complete cDNA probes. Consistent with the deletion locations described previously, the deletions of dystrophin gene in Chinese individuals are clustered mainly in two high-frequency deletion regions of exons 44-52 (68.6%) of 3' side of the gene central regions and exons 1-19 (26.7%) in the 5' side. The distribution of deletions in dystrophin gene is associated with the phenotype of DMD/BMD. In the 25 cases with in-frame deletions, 15 deletions located in the region of exons 2-47 were milder BMD and intermediate patients, as the location of deletions was not the important region of the dystrophin gene.
Human genome sequencing is accelerating rapidly. Multiple genome maps link this sequence to problems in biology and clinical medicine. Because each map represents a different aspect of the structure, content, and behavior of human chromosomes, these fundamental properties must be integrated with the genome to understand disease genes, cancer instability, and human evolution. Cytogenetic maps use 400-850 visible band landmarks and are the primary means for defining prenatal defects and novel cancer breakpoints, thereby providing simultaneous examination of the entire genome. Recent genetic, physical, and transcript maps use PCR-based landmarks called sequence-tagged sites (STSs). We have integrated these genome maps by anchoring the human cytogenetic to the STS-based genetic and physical maps with 1021 STS-BAC pairs at an average spacing of approximately 1 per 3 Mb. These integration points are represented by 872 unique STSs, including 642 polymorphic markers and 957 bacterial artificial chromosomes (BACs), each of which was localized on high resolution fluorescent banded chromosomes. These BACs constitute a resource that bridges map levels and provides the tools to seamlessly translate questions raised by genomic change seen at the chromosomal level into answers based at the molecular level. We show how the BACs provide molecular links for understanding human genomic duplications, meiosis, and evolution, as well as reagents for conducting genome-wide prenatal diagnosis at the molecular level and for detecting gene candidates associated with novel cancer breakpoints.
A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Use of antibiotics for acute respiratory infection (ARI) of presumed viral etiology is a worldwide problem. The World Health Organization (WHO) has provided guidelines for diagnosis and treatment of ARI for developing countries. METHODS: Specially trained observers applied the WHO criteria to study the diagnosis and treatment of ARI given by 100 randomly selected health care workers (HCWs) in a rural county in China. A total of 750 cases of ARI were evaluated. RESULTS: Before the parents sought medical care, 47% of children in the county hospitals, 25% of those in the townships and 18% of those in the villages had already received antibiotics, available without prescription. Among the HCWs antibiotic abuse (antibiotics for presumably viral disease) was detected in the treatment of 97% of cases, and severe abuse (such as prescription of two incompatible antibiotics) was detected in 37%. Most (197 of 200) patients with bacterial disease received antibiotics, but inappropriate antibiotic treatment (dose or type) was observed in 63% of these cases. HCWs with university training and those with higher test scores on knowledge and attitude prescribed antibiotics more judiciously than those lacking those attributes. CONCLUSIONS: Abuse of antibiotics for ARI is a serious and costly problem in rural China, potentially leading to widespread antibiotic resistance. Educating HCWs in the management of ARI and proper use of antibiotics has high priority in China.
Completion of genetic and physical maps requires markers from the ends (telomeres) of every human chromosome. We have searched for short tandem repeats (microsatellites) in cosmid and P1 clones and generated 661 sequence-tagged sites (STS) from the terminal 300 kb of 31 human chromosome ends. PCR assays were successfully designed for 58 microsatellites and mapped both genetically and on radiation hybrids (RHs) to confirm their telomeric location. Sequence analysis revealed marked variation in sequence composition, consistent with the hypothesis that even very highly GC-rich chromosome bands (the T bands) are not homogenous. The STSs that we have generated will be a necessary resource for the construction of physical maps of these complex regions of the genome.
In islet cells isolated from normal outbred Wistar rats, the known high vulnerability of islet cells toward oxygen radicals or nitric oxide can be abolished by inducing a stress response, such as by heat shock. We show here that islet cells from diabetes-prone BB rats are unable to mount such a protective response. Islet cells from diabetes-prone BB rats without recognizable insulitis were heat stressed. Subsequently, cells were exposed to nitric oxide, to oxygen radicals, or to the beta-cell toxin streptozotocin. While prior heat shock substantially increased the survival of toxin-treated Wistar rat islet cells, no protective stress response was noted for islet cells from diabetes-prone BB rats. Islet cells from diabetes-resistant BB rats were protected by heat stress to the same extent as Wistar rats. A survey of four additional major histocompatibility complex (MHC)-disparate rat strains confirmed the existence of a low and high responder type to stress. Parallel analysis of heat shock protein (hsp)70 induction by Western blot showed a low and high hsp70 response phenotype. A high hsp70 response coincided with a protective stress response. The presence (or absence) of a protective stress response correlated with the preservation (or loss) of intracellular NAD+ in toxin-treated islet cells. The lack of a protective stress response in islet cells from diabetes-prone BB rats, but not in diabetes-resistant BB rats, may promote beta-cell lysis and autoantigen release, and hence could be important for initiation or propagation of the disease process.
17 subjects highly susceptible to motion sickness were divided into Nausea and No-nausea groups depending upon whether the subjects experienced nausea during adaptation to nauseagenic rotation. Eight subjects in the Nausea group viewed an optokinetic rotation drum for repeated sessions of 16 min., with an interval of two days between every two sessions. During each session the subjects continuously viewed the rotating drum 16 min. even if they experienced nausea. nine subjects in the No-nausea group likewise viewed an optokinetic rotation drum for at most 16 min. but immediately stopped viewing the rotating drum whenever they experienced nausea during the session. The criteria for full adaptation were that the subject reported no feelings of stomach discomfort and nausea during a 16-min session. The mean number of sessions to reach full adaptation was 3.9 (SD = 0.6) with a range 3 to 5 sessions for the subjects in the Nausea group and 3.2 (SD = 0.8) with a range 2 to 4 for the subjects in the No-nausea group. It was concluded that subjects can adapt to a nauseagenic optokinetic rotation by repeated exposure without experiencing nausea and vomiting during adaptation.
The pharmacological and toxic actions of raw Fructus Psoraleae and its salt-baked, and improved salt-baked products were comparatively studied. The leucogenic action of the improved salt-baked product was more effective than that of the original salt-baked one. But no significant difference in antidiarrheal or antiandrogenoid effect was found between the two salt-baked products. The toxicity(LD50 and the injury on kidney) of the improved salt-baked product was lower than that of the salt-baked. one. The results indicate that this improved processing method would contribute to increasing the efficacy and decreasing the toxicity of Fructus Psoraleae.
To evaluate the safety and efficacy of weekly low-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory cancer, participating subjects received standard prophylactic medication followed by intravenous paclitaxel once a week for 3 weeks every 4 weeks. The 50-mg/m2 starting dose was increased by 10 mg/m2 for every five patients, as long as no dose-limiting toxicity had occurred in more than two of five patients treated at the preceding level. Eligibility criteria included metastatic and refractory malignant disease; an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; and adequate hematologic, hepatic, and renal functions. Of 30 patients treated and evaluable for toxicity, 25 were evaluable for response. The majority of patients tolerated the treatment very well. In a total of 114 cycles, the worst toxicities observed were leukopenia (one grade 4, two grade 3), granulocytopenia (one grade 3, one grade 4), anemia (one grade 3, two grade 2), and infection (one grade 5, one grade 3). Three patients had grade 2 gastrointestinal toxicity and three had grade 1 peripheral neuropathy. Only one dose-limiting toxicity, at 100 mg/m2, has occurred. This patient died of bilateral pneumonia with neutropenia. We have observed partial responses in seven of 12 patients with breast cancer and three of eight with non-small cell lung cancer. The study remains open at the current dose level of 100 mg/m2/wk. Weekly low-dose paclitaxel is well tolerated and efficacious. Further phase II studies are warranted, to continue evaluation of this schedule of paclitaxel either alone or in combination with other drugs active in paclitaxel-responsive diseases.
The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.
Explore the source record for details and available documents.
Four of 55 (7%) adult acute lymphocytic leukemia patients, age 27-58 years, who were treated with methotrexate, vincristine, L-asparaginase, and dexamethasone (MOAD) developed avascular necrosis (AVN) of one or both femoral heads 16-39 months after beginning treatment. All patients were treated with total joint replacement without compromise of quality of life during more than 3-9 years of follow-up, and they have remained in complete remission for a total of 6.5 + to 10.5 + years. A review of the literature revealed 11 previously reported cases of AVN of bone in patients with acute lymphocytic leukemia, 10 of whom received dexamethasone. The patients in the present report received a total dexamethasone dose equivalent to that of prednisone, 3.4-5.0 g/M2. Although AVN of bone has been reported in patients receiving chemotherapy without corticosteroids, corticosteroids appear to be the most common class of agents associated with its development, and dexamethasone treatment may be more likely to result in AVN of bone than other corticosteroids, for unknown reasons.
Explore the source record for details and available documents.