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Biomedical subjects

R Kim

Publications and source records attributed to R Kim.

At least 127 records · Page 7Linked to original sources

Efficacy of cisplatin, 5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus.

Eighteen patients with esophageal carcinoma (16 adenocarcinoma, two squamous cell carcinoma) were treated with two cycles of induction chemotherapy consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 (3-hour infusion), cisplatin 20 mg/m2/d x 4 days, and 5-fluorouracil 1 g/m2/d (continuous infusion x 4 days) separated by a 28-day interval before surgical resection. After resection, patients received two more cycles of the same regimen. A thorough staging evaluation was performed before patients were enrolled in the study. The salient chemotherapy toxicities included grade 3 nausea (two patients), grade 3 vomiting (two patients), grades 3 and 4 diarrhea (one patient each), and grades 3 and 4 neutropenia (two and 10 patients, respectively). No deaths occurred due to toxicity. Surgical resection was attempted in all 18 patients (100%) after two cycles of induction chemotherapy. Esophageal resection was successfully completed in 17 patients. Liver metastases were noted at laparotomy in the one patient who subsequently did not undergo esophageal resection. Surgical complications were minor, and no postoperative deaths occurred. Fifteen patients received two additional cycles of the paclitaxel/5-fluorouracil/cisplatin regimen postoperatively, two received only one cycle, and one refused further therapy. Of 15 patients alive, 14 show no evidence of disease. The 1-year actuarial survival rate of this group of patients is 82%. In conclusion, the paclitaxel/5-fluorouracil/cisplatin combination is well tolerated and is an active regimen in esophageal carcinoma.

Adenocarcinoma↗

Morphologic, histologic, and molecular similarities between adenocarcinomas arising in the gastric stump and the intact stomach.

BACKGROUND: Patients with gastric remnants resulting from partial resections have an increased risk for carcinoma. It is unclear whether adenocarcinoma arising in the gastric stump (GSca) differs from intact stomach carcinoma (Gca). The goal of this study was to examine the pathologic and molecular features of GSca and compare them with Gca. METHODS: Adjacent nonmalignant areas and tumors from 14 patients who were 19-55 years postgastrectomy (mean, 32.1 years) were compared with 14 Gca by pathologic and molecular analysis. Formalin fixed, paraffin embedded specimens were immunohistochemically stained for p53 followed by topographic genotyping. Exons 5-8 were amplified by the polymerase chain reaction and directly sequenced. RESULTS: No differences were noted between the two groups regarding gender, types of metaplasia, dysplasia, morphology, or histologic tumor type. However, a higher incidence of cystic dilatation and foveolar hyperplasia were present in GSca. p53 gene point mutations occurred in 5 of 14 (35.7%) GSca patients. GSca p53 mutations included missense point mutations (G:A transitions in four patients and G:C transversion in one patient) with allelic loss. In four of the five patients with p53 mutations, the same mutation was also observed in the adjacent area. p53 point mutations were present in 4 of 14 Gca (28.6%), in exons 5, 6, and 8. In one case, the same mutation was also detected in the adjacent nonmalignant mucosa. CONCLUSIONS: Similarities in clinical, pathologic, and molecular features between GSca and Gca suggest the possibility that they share similar mechanisms of carcinogenesis. p53 gene alterations in premalignant areas may denote a possible early role of this gene in gastric carcinoma.

Adenocarcinoma↗

A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study.

OBJECTIVE: To determine whether low-level lead exposure is associated with impaired renal function. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Subjects were 459 men randomly selected from the participants of the Normative Aging Study who were originally recruited from healthy veterans in the greater Boston area in 1961 and were periodically examined at the Department of Veterans Affairs Outpatient Clinic every 3 to 5 years. We reconstructed blood lead concentrations for the period between 1979 and 1994 using samples of either archived red blood cells or fresh whole blood. MAIN OUTCOME MEASURES: Serum creatinine concentration. RESULTS: After adjustment for age, body mass index, smoking, alcohol consumption, educational level, and hypertension, blood lead concentration was positively and significantly associated with concurrent concentration of serum creatinine (P=.005). A 10-fold increase in blood lead level predicted an increase of 7 micromol/L (0.08 micrograms/dL) in serum creatinine concentration, which is roughly equivalent to the increase predicted by 20 years of aging. The association was also significant among subjects whose blood lead concentrations had never exceeded 0.48 micromol/L (10 micrograms/L) throughout the study period. The age-related increase in serum creatinine level was earlier and faster in the group with the highest-quartile levels of long-term lead exposure than in the group with the lowest-quartile levels. CONCLUSIONS: Low-level exposure to lead may impair renal function in middle-aged and older men. Longitudinal data suggest an acceleration of age-related impairment of renal function in association with long-term low-level lead exposure.

Age Factors↗

Regulation of involucrin gene expression by calcium in normal human keratinocytes.

Calcium is essential for normal epidermal differentiation. Data from Northern and nuclear run-on analysis indicate that involucrin gene transcription is induced by 1.2 mM extracellular calcium. A 3.7 Kbp fragment of the involucrin gene, which contains 2.5 Kbp of upstream region, the transcription start site, and the first intron, was sub-cloned into the pGL3-basic luciferase reporter vector and transfected into pre-confluent normal human keratinocytes (NHK). The stimulated activities of this clone were above basal levels and was further enhanced eight-fold by 1.2 mM extracelluar calcium. The results from a series of truncation and internal deletion experiments revealed multiple calcium-independent enhancer elements between -2476 and -2131 bp of the transcription start site and a calcium-dependent element between -2131 and -2028 bp. This 103 bp fragment contains sequences of an AP-1 site (TGAGTCA), a SP-1 site (GGGCGG), and shares homology with two elements in the human keratin-1 promoter, within the regions identified as mediating the calcium responsiveness of that gene in keratinocytes. One or more of these putative elements may be involved in the calcium-dependent regulation of the involucrin gene transcription in NHK.

5' Flanking Region↗

Comparative p53 mutational analysis of multiple primary cancers of the upper aerodigestive tract.

BACKGROUND: Tumors arising in the upper aerodigestive tract (UAT) are often associated with predisposing factors that place the patient at risk for development of multiple synchronous or metachronous tumors. The aim of this study was to evaluate p53 as a susceptibility gene in UAT malignancy. METHODS: Seventeen patients with 41 separate primary tumors involving esophagus (n = 15), larynx (n = 14), pharynx (n = 6), lung (n = 2), mouth (n = 2), and tongue (n = 2) were analyzed for the presence and specific genotype of p53 point mutation. Immunohistochemical staining of p53 and topographic genotyping consisting of polymerase chain reaction amplification and direct sequencing of p53 exons to 5 to 8 were performed. RESULTS: Eleven tumors were metachronous (6 months to 11 years), and 11 were synchronous. We found p53 point mutations in 19 (46.3%) of 41 tumors in exons 8 (n = 11), 7 (n = 4), 5 (n = 3), and 6 (n = 1). Tumors possessed either wild-type p53 or a single type of point mutation. Metastases displayed the identical genotype of its primary tumor in all cases. Most importantly, p53 genotype was found to be completely discordant between separate primary tumors for the same patient. CONCLUSIONS: Complete discordance in p53 genotype between separate primary UAT cancers strongly indicates that p53 is not functioning as a susceptibility gene in this setting.

Adult↗

Applications of the World Wide Web to neurosurgical practice.

OBJECTIVE: The objectives of the New York University (NYU) neurosurgery Web resource are the following: 1) to educate patients and families of patients who have neurosurgical problems, 2) to provide a forum for communication among neurosurgeons and other physicians, 3) to educate neurosurgeons, and 4) to provide neurosurgeons with resources for enhancing their practices. METHODS: The NYU neurosurgery Web resource resides on a Sun SparcStation 20, running Solaris 1.0 and National Center for Supercomputing Applications httpd 1.0. It is aimed at a broad audience that includes the general public as well as practicing neurosurgeons and other physicians. Accordingly, general information regarding a variety of neurosurgical problems is presented in easy-to-understand language. Material intended specifically for neurosurgeons, such as case discussions, is designed to stimulate discussion and encourage outside submissions. Interaction with the NYU faculty and residents may be accomplished by using electronic mail, file transfer protocol, and direct Web postings. Media in development include java applets and real-time video over the Internet. The uniform resource locator for the NYU neurosurgery Web site is "http:/(/)mcns10.med.nyu.edu/". RESULTS: The Web site has averaged 1800 accesses per month, and 5 to 10 electronic mail messages are received daily. Several patients for whom our faculty have held consultations over the Web have undergone surgery at NYU. The most popular areas of the Web site are the spinal surgery section and the brain tumors section. CONCLUSION: The ability to capitalize on the World Wide Web as a facile user is becoming an increasingly important skill for the modern neurosurgeon. In addition, Web sites published by neurosurgeons offer opportunities for communication and consultation that have previously been impossible.

Computer Communication Networks↗

Isolation and cDNA cloning of Ksp-cadherin, a novel kidney-specific member of the cadherin multigene family.

Cadherins are recognized as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. We report here the identification of a structurally unique, kidney-specific member of the cadherin multigene family (Ksp-cadherin). cDNA cloning and molecular analysis of the 130-kDa protein confirmed that it was novel and indicated that it most closely resembled members of the LI-cadherin/HPT-1 cadherin subgroup. The predicted protein possesses the definitive cadherin-specific sequence motifs LDRE, DXND, and DXD in well conserved sequential arrangement, and the characteristic cysteine residues found in the last ectodomains of almost all known cadherins. Like LI-cadherin and HPT-1, Ksp-cadherin lacks the prosequence and HAV adhesion recognition sequence typical of most classical cadherins, and possesses a truncated cytoplasmic domain (18-22 amino acids). When expressed in a transient Vaccinia/T7 expression system, Ksp-cadherin displayed the classic calcium sensitivity to trypsin proteolysis that is observed in all cadherins. Immunolocalization studies and Northern analysis indicated that expression of Ksp-cadherin was kidney-specific and limited to the basolateral membranes of renal tubular epithelial cells. In summary, we have identified and cloned a novel, kidney-specific member of the cadherin multigene family that we propose be designated Ksp-cadherin.

Amino Acid Sequence↗

Axillary node status in nonpalpable breast cancer.

BACKGROUND: The metastatic status of the axillary nodes is prognostically important but its value has been questioned in the management of nonpalpable breast tumors. This study correlates the incidence of positive nodes with the size of the primary nonpalpable tumors. METHODS: We retrospectively analyzed 220 invasive and 21 microinvasive breast cancers that were excised after needle localization and for which axillary dissections were subsequently performed. Of invasive cancers, 166 presented as mass lesions with or without microcalcifications and 54 as microcalcifications alone. The size of the mass lesions (n = 166) was determined mammographically and on pathologic specimens. They were subdivided into five groups according to diameter: (a) < or = 5 mm, (b) 6-10 mm, (c) 11-20 mm, (d) > 20 mm, and (e) unrecorded size. RESULTS: Axillary metastases were found in 9% of patients whose cancer presented as microcalcifications alone. They were found in 0, 11, and 22% of patients in mammographic groups, a, b, and c, respectively. In the corresponding groups in which size was determined from the pathology report, metastases were found in 5, 10, and 27%. CONCLUSION: The size of nonpalpable breast cancers measured on the excised gross specimen and by mammogram accurately predicts the likelihood of axillary node metastasis.

Axilla↗

Quantitative endoscopy: precise computerized measurement of metaplastic epithelial surface area in Barrett's esophagus.

BACKGROUND/AIMS: The inability to precisely measure the area of Barrett's metaplasia has impaired the study of its natural history and response to therapy. This study used a novel computer program that creates two-dimensional maps of the esophagus allowing for calculation of the area of Barrett's metaplasia. METHODS: Endoscopic photographs of Barrett's models and patients were obtained by independent endoscopists. The program transformed the photographs into maps, and the area of Barrett's metaplasia was calculated. RESULTS: Using models, calculated areas correlated with actual areas (r = 0.96) with an overall error of 5.2%. Color, size, shape, diameter of the model, or endoscopist's experience did not affect the accuracy. Accuracy did improve by decreasing the interval between photographs from 4 cm (10.0% error) to 2 cm (4.8% error). In patients, area calculations from maps created by independent technicians correlated precisely (r = 0.99) at 1-cm (n = 22) and 2-cm (n = 40) intervals. Independent endoscopists correlated precisely in producing photographs for map construction (r = 0.99; n = 20). CONCLUSIONS: This novel computer technology produces two-dimensional maps of Barrett's metaplasia that can be used to accurately calculate area. Minimal interobserver variability in obtaining photographs is found.

Adult↗

House dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus) prevalence in the rooms and hallways of a tertiary care hospital.

BACKGROUND: House dust mites, Dermatophagoides farinae and Dermatophagoides pteronyssinus, are important components in the development of asthma. OBJECTIVE: We measured the prevalence of house dust mites in a tertiary care hospital located in a temperate geographic region where dust mites were prevalent in homes. METHODS: The density of Dermatophagoides spp. was measured in hospital hallways, carpeted patients' rooms, and noncarpeted patients' rooms by vacuuming the floor in the summer and winter seasons. Bedrooms in the homes of employees were sampled as a summer control group. A total of 141 dust samples was obtained. RESULTS: No D. farinae or D. pteronyssinus was found in 60 hospital dust samples that were obtained during the winter season. Although mites were found in some locations in the hospital during the summer dust collection, mite density in these locations and the average mite density for all samples were insignificant. During the summer dust samples from the bedroom carpets of all employees' homes sampled were positive for mites, with many homes having moderate or high populations (range, 22 to 8340 mites per gram of dust). CONCLUSIONS: The dust mite prevalence in a hospital could be kept very low even though mite levels in employees' homes were moderate to high. The factors responsible for the low mite density in the hospital were maintenance of low relative humidity, use of low-pile carpets, and good housekeeping and laundering practices.

Animals↗

K x-ray fluorescence measurements of bone lead concentration: the analysis of low-level data.

K line x-ray fluorescence (KXRF) measurements of bone lead have emerged as a promising new biological marker of internal lead dose in epidemiological studies. Some disagreements exist, however, over the analysis of data at low levels of bone lead concentration. In this study, we performed 30 serial measurements on each of three phantoms containing spiked amounts of lead. Chemical analysis of these phantoms using an inductively coupled plasma mass spectrometer (ICPMS) indicated that the lead concentrations were 0.30, 5.77, and 11.57 micrograms g-1. Analysis of the data was performed using several definitions of a minimum detectable limit (MDL) to recode data below the MDL, and using all of the continuous point estimates of lead concentration in the phantom (including negative estimates). The results demonstrate that the use of MDLs to recode low-level observations reduces the efficiency of the analysis and the ability to distinguish between the phantoms. Retaining all point estimates of KXRF-measured bone lead concentration provides less bias and greater efficiency in comparing the mean or median levels of bone lead of different populations.

Analysis of Variance↗

SPECT in dementia: clinical and pathological correlation.

BACKGROUND: The clinical diagnosis of dementia continues to be flawed. Although the diagnosis of Alzheimer's disease (AD) is better than 90% at research centers in highly selected patients, the diagnosis of patients with non-AD dementias and atypical AD patients is poor. Single photon emission computed tomography (SPECT) is a functional imaging technique touted as a diagnostic technique for the degenerative disorders. However there have been few clinicopathological studies using SPECT. METHODS: Twenty-seven consecutive dementia patients were evaluated clinically at a University-based specialty dementia clinic, and a diagnosis of a specific dementia was made. SPECT imaging was used in helping to select a clinical diagnosis. The correlations between clinical, SPECT and autopsy diagnoses were analyzed. RESULTS: Single photon emission computed tomography predicted pathologic diagnosis in 25 of 27 patients with dementia (92.6%), compared with clinical diagnosis, which was confirmed in 20/27 (74.1%). Distinct patterns were associated with dementia caused by AD, Fronto-Temporal Dementia (FTD), and Jakob-Creutzfeldt Disease (JCD). Vascular insults not seen with computerized tomography (CT) or magnetic resonance imaging (MRI) were found with SPECT. Three different pathologies were found in patients with Parkinsonian-Dementias (PD): Lewy-Body Variant of AD, Diffuse Lewy-bodies without plaques, and substantia nigra neuronal loss without plaques or Lewy-bodies. All showed a temporal-parietal pattern with SPECT that was similar to AD. CONCLUSION: SPECT provides useful positive information in dementia, particularly the differentiation of AD, FTD, and JCD. However, it does not distinguish PD from AD.

Adult↗

A longitudinal study of chronic lead exposure and physical growth in Boston children.

We investigated the cross-sectional and longitudinal relationships between chronic exposure to lead and physical growth among a cohort of children reassessed 13 years after initial examination. We measured weight, height, and dentin lead levels of 270 children in 1975-78. In 1989-1990 we reexamined 79 of these children for measurement of weight, height, and bone lead levels by means of in vivo K X-ray fluorescence. To avoid potential confounding by race and chelation history, analysis was restricted to white subjects without a history of lead chelation therapy. A total of 236 subjects provided complete information for the study of cross-sectional relationship between dentin lead levels and changes in physical growth: 58 subjects for the study of longitudinal relationship between dentin lead levels and changes in physical growth and 54 subjects for the study of longitudinal relationship between bone lead levels and changes in physical growth. Dentin lead levels averaged 14.9 micrograms/g; tibia and patella lead levels averaged 1.2 and 5.0 micrograms/g, respectively. With control for potential confounders including age, sex, baseline body size, and mother's socioeconomic status, log10 dentin lead level was positively associated with body mass index as of 1975-1978 (beta = 1.02, p = 0.03) and increase in body mass index between 1975-78 and 1989-90 (beta = 2.65, p = 0.03). Bone lead levels were not significantly associated with physical growth. This is the first study relating chronic lead exposure to body mass index. The results suggest that chronic lead exposure in childhood may result in obesity that persists into adulthood.

Adolescent↗

Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression.

We performed a randomised trial on 37 hips (33 patients) with early-stage osteonecrosis (ON). After the initial clinical evaluation, including plain radiography and MRI, 18 hips were randomly assigned to a core-decompression group and 19 to a conservatively-treated group. All the patients were regularly followed up by clinical evaluation, plain radiography and MRI at intervals of three months. Hip pain was relieved in nine out of ten initially symptomatic hips in the core-decompression group but persisted in three out of four initially painful hips in the conservatively-treated group at the second assessment (p < 0.05). At a minimum follow-up of 24 months, 14 of the 18 core-decompressed hips (78%) and 15 of the 19 non-operated hips (79%) developed collapse of the femoral head. By survival analysis, there was no significant difference in the time to collapse between the two groups (log-rank test p = 0.79). Core decompression may be effective tin symptomatic relief, but is of no greater value than conservative management in preventing collapse in early osteonecrosis of the femoral head.

Adolescent↗