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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 55 records · Page 3Linked to original sources
PubMed2001

Successful use of high dose rate brachytherapy for non-malignant bronchial obstruction.

High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused symptomatic occlusion of the airway, necessitating multiple laser applications. A single treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy. The patient remains well 15 months after treatment with no evidence of recurrent granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective treatment for non-malignant airway obstruction.

Adult↗
PubMed2001

Repeatability characteristics of simple indices of insulin resistance: implications for research applications.

The objectives of this study were to evaluate test characteristics, such as normality of distribution, variation, and repeatability, of simple fasting measures of insulin sensitivity and to use the results to choose among these measures. Duplicate fasting samples of insulin and glucose were collected before 4 h of euglycemic hyperinsulinemic clamping using insulin infusion rates ranging from 40-600 mU/m2 x min. Currently recommended estimates of insulin sensitivity, including the fasting insulin, 40/insulin, the homeostasis model assessment, the logarithmic transformation of the homeostasis model assessment, and the Quantitative Insulin Sensitivity Check Index, were evaluated. The normality of distribution and the variability of the tests (coefficient of variation and discriminant ratio) were compared between the measures and against the "gold standard" hyperinsulinemic clamp. Data from 253 clamp studies in 152 subjects were examined, including 79 repeated studies for repeatability analysis. In subjects ranging from lean to diabetic, the log transformed fasting measures combining insulin and glucose had normal distributions and test characteristics superior to the other simple indices (logarithmic transformation of the homeostasis model assessment coefficient of variation, 0.55; discriminant ratio, 13; Quantitative Insulin Sensitivity Check Index coefficient of variation, 0.05; discriminant ratio, 10) and statistically comparable to euglycemic hyperinsulinemic clamps (coefficient of variation, 0.10; discriminant ratio, 6.4). These favorable characteristics helped explain the superior correlations of these measures with the hyperinsulinemic clamps among insulin-resistant subjects. Furthermore, therapeutic changes in insulin sensitivity were as readily demonstrated with these simple measures as with the hyperinsulinemic clamp. The test characteristics of the logarithmic transformation of the homeostasis model assessment and the Quantitative Insulin Sensitivity Check Index are superior to other simple indices of insulin sensitivity. This helps explain their excellent correlations with formal measures both at baseline and with changes in insulin sensitivity and supports their broader application in clinical research.

Adult↗
PubMed2001

Diminished skin blood flow in Type I diabetes: evidence for non-endothelium-dependent dysfunction.

The purpose of this study was to quantify the extent to which skin blood flow (SBF) responses to application of endothelium-dependent and -independent vasodilating agents differ between Type I diabetic patients and healthy subjects. Patients and matched controls were studied after an overnight fast. SBF was determined with laser Doppler perfusion imaging before and after iontophoresis of acetylcholine (Ach; endothelium-dependent) and sodium nitroprusside (SNP; endothelium-independent). Basal SBF did not differ significantly between groups. Iontophoresis of ACh and SNP increased SBF 20-fold in controls. In the patients, the increases in SBF following iontophoresis of ACh and SNP were reduced by 18% and 19%, respectively, versus controls (P<0.05 for both). These data demonstrate that Type I diabetic patients have similar diminished SBF responses to iontophoresis of ACh and SNP, which suggests that non-endothelial-dependent factors are primarily responsible for the diminished SBF responses.

Acetylcholine↗
PubMed2001

Making decisions about cancer screening when the guidelines are unclear or conflicting.

OBJECTIVE: Our purpose was to determine the factors involved in the cancer screening decisions of family physicians in situations where the clinical practice guidelines are unclear or conflicting as opposed to when they are clear and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups using a constant comparative approach. POPULATION: A total of 73 family physicians in active practice participated in 10 focus groups (1 urban group and 1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main outcome measures were participants' perceptions regarding cancer screening when the guidelines were unclear or conflicting. RESULTS: We propose a model of the determinants of cancer screening decision making with regard to unclear and conflicting guidelines. This model is rooted in the physician-patient relationship, and is an interactive process influenced by patient factors (anxiety, expectations, and family history) and physician factors (perception of guidelines, clinical practice experience, influence of colleagues, distinction between the screening styles of specialists and family physicians, and the amount of time and financial costs involved in performing the maneuver). CONCLUSIONS: Our model is unique, because it is embedded in the physician-patient relationship. Ultimately, a modified model could be used to design interventions to assist with the implementation of preventive services guidelines.

Adult↗
PubMed2000

Quantification of intracavitary brachytherapy parameters and correlation with outcome in patients with carcinoma of the cervix.

PURPOSE: To quantify the M. D. Anderson criteria for acceptable implant geometry; to relate our system of intracavitary radiotherapy (ICRT) prescription to Manchester and ICRU reference doses; and to correlate these parameters with outcome measures. METHODS AND MATERIALS: The relationships between intracavitary applicators and normal structures were measured directly from localization films of 808 applications performed in 396 patients who completed definitive treatment for cervical cancer between 1990 and 1994. The distances between applicators and tissue landmarks and the doses to Manchester and normal tissue reference points were correlated with outcome. RESULTS: The median distance from the tandem to the sacrum was 4.0 cm, or one-third the distance from the pubis to the sacrum. The mean distance between the vaginal ovoids and cervical marker seeds was 7 mm, and the median distance between the tandem and the posterior edge of the ovoids was 50% of the ovoid length. In 92% of insertions, vaginal packing was posterior to or within 5 mm of a line that passed through the posterior edge of the ovoids, parallel to the tandem. The median doses to Point A and rectal, bladder, and vaginal surface reference points were 87 Gy, 68 Gy, 70 Gy, and 125 Gy, respectively. Although these reference doses were not routinely used to prescribe treatment, consistent applicator geometry and source selection resulted in a relatively narrow range of delivered doses. The average ratios between the doses at bladder or rectal reference points and Point A were somewhat greater when smaller vaginal applicators were used. Patients received a median of 5600 mgRaEq-h from ICRT. The total mgRaEq-h were correlated with but were not proportional to the dose at Point A. There were no significant correlations between the doses to standard reference points and the rates of central recurrence or major complications. CONCLUSION: When ICRT implants are carefully placed, relatively high paracentral doses can be delivered that yield a high rate of central disease control with an acceptable rate of complications. The narrow range of doses delivered to standard reference points and their inconsistent correlation with the maximum doses delivered to normal tissues probably contributed to a lack of correlation between reference doses and outcome.

Adult↗
PubMed2000

Blood-based RT-PCR assays of MN/CA9 or PSMA: clinical application in renal cancer patients.

OBJECTIVES: To report a survey of blood-based RNAs obtained from common groups of control and renal cancer patients for expression of both MN/CA9 and prostate-specific membrane antigen (PSMA) messenger RNAs. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) assays for MN/CA9 and PSMA were performed on RNAs extracted from 81 blood samples (59 patients with renal cancer, 7 with benign tumors, and 15 control volunteers). The results of these assays were statistically analyzed to determine whether a positive result (individually or combined) correlates with any tumor characteristics. RESULTS: Neither MN/CA9 nor PSMA amplification products were detected in the RNAs from peripheral blood samples of the 15 control volunteers and from the 7 patients with benign renal tumor (sensitivity 100%). MN/CA9 alone was detected in 11 (19%) of 59 samples and PSMA alone in 12 (20%) of 59 samples from patients with renal cancer. PSMA positivity was significantly correlated with vascular invasion of the primary tumor. Expression of one or both of these molecular tumor markers was detected in 21 (36%) of 59 renal cancer patients. When combined, the results of the MN/CA9 and PSMA RT-PCR tests were found to be highly associated with vascular invasion in nephrectomy specimens (sensitivity 67%, specificity 77%, odds ratio = 6.89, P = 0.002). CONCLUSIONS: Combination of RT-PCR assays for MN/CA9 and PSMA provides a sensitive blood test for molecular detection of clear cell carcinoma of the kidney and its potential for vascular invasion. Further testing of this assay will be required to evaluate its efficacy in the diagnosis, screening, and follow-up of patients with kidney cancer.

Adult↗
PubMed2000

[Breast cancer after mantle field irradiation for Hodgkin's disease].

Effective use of modern therapeutic modalities results in the cure of 75%-80% of Hodgkin's disease patients, regardless of stage. The major threat to continued survival is, therefore, not recurrent disease but development of second malignancies. Recent reports have firmly established the increased risk of breast cancer developing in women treated with mantle field irradiation. We describe 3 women who developed breast carcinoma following mantle field irradiation for Hodgkin's disease. Their clinical course was consistent with that reported in larger series. They were relatively young when irradiated and there was a long interval between radiation therapy and the diagnosis of breast cancer. Review of the literature shows that there may be a role for prophylactic mastectomy after irradiation for Hodgkin's disease.

Adult↗
PubMed2000

Socioeconomic characteristics of patients with squamous cell carcinoma of the uterine cervix treated with radiotherapy in the 1992 to 1994 patterns of care study.

PURPOSE: To describe the relationship between socioeconomic variables and the treatment of patients with radiotherapy for cervix cancer.40% minority patients. METHODS AND MATERIALS: Sixty-two institutions werw r andomly selected from a list of all radiotherapy facilities in the Unite d States. From these we randomly selected and reviewed 471 cases of squ amous cell carcinoma treated during 1992 to 1994. To create an addition al minority-rich sample, we randomly selected 215 additional cases from 17 randomly selected institutions that admitted >40% minority patients. The median household income of each patient's neighborhood was determined by matching her zip code to data from the 1990 United States Census. RESULTS: Pati ents who lived in low-income neighborhoods, who had only Medicaid covera ge, or who were treated at large academic or minority-rich institutions tended to have a poorer initial performance status, higher-stage or bulk y central disease, and a lower pretreatment hemoglobin level. Ability t o complete treatment did not correlate with ethnicity or income. Howeve r, noncompliant patients tended to be treated at minority-rich instituti ons and were more often < 40 or > 60 years old. Patients who completed definitive treatment were more likely to have had </= 1 low-dose-rate intracavitary implants if they were black, came from a low-income neighborhood, were covered by Medicaid or Medicare only, or were treated at a minority-rich institution. Patients who were treated in academic institutions received higher mean radiation doses to Point A (83.8 Gy) than those treated in research- or non-research-participating facilities (79.4 and 80.9 Gy, respectively; p = 0.002). Patients who received their radiation therapy in facilities that treated an average of </= 3 patients per year also received lower mean doses to Point A (79.1 vs. 83.0 Gy; p = 0.001). CONCLUSION: The treatment received by patients who belonged to minority groups, came from low-income neighborhoods, or were treated in large, minority-rich institutions differed in several respects from that of white, higher income patients. Larger, more detailed studies will be needed to clarify the reasons for these differences and to define any influence on treatment outcome.

Adult↗
PubMed2000

Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties.

Insulin resistance in the liver and peripheral tissues, together with a pancreatic cell defect, are the common causes of Type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibition of PTPases may be an effective method in the treatment of Type 2 diabetes. We have identified two novel series of benzofuran/benzothiophene biphenyl oxo-acetic acids and sulfonyl-salicylic acids as potent inhibitors of PTP1B with good oral antihyperglycemic activity. To assist in the design of these inhibitors, crystallographic studies have attempted to identify enzyme inhibitor interactions. Resolution of crystal complexes has suggested that the inhibitors bind to the enzyme active site and are held in place through hydrogen bonding and van der Waals interactions formed within two hydrophobic pockets. In the oxo-acetic acid series, hydrophobic substitutents at position-2 of the benzofuran/benzothiophene biphenyl framework interacted with Phe182 of the catalytic site and were very critical to the intrinsic activity of the molecule. The hydrophobic region of the catalytic-site pocket was exploited and taken advantage by hydrophobic substituents at either the alpha-carbon or the ortho aromatic positions of the oxo-acetic acid moiety. Similar ortho aromatic substitutions on the salicylic acid-type inhibitors had no effect, primarily due to the different orientation of these inhibitors in the catalytic site. The most active inhibitors of both series inhibited recombinant human PTP1B with phosphotyrosyl dodecapeptide TRDI(P)YETD(P)Y(P)YRK as the source of the substrate with IC(50) values in the range of 20-50 nM. Compound 68 was one of the most active compounds in vivo, normalizing plasma glucose levels at the 25 mg/kg dose (po) and the 1 mg/kg dose (ip). Compound 68 was also selective against several other PTPases.

Administration, Oral↗
PubMed2000

[High dose endobronchial brachytherapy for malignant airway obstruction: first study of 30 patients].

Brachytherapy is especially suitable for palliative treatment of endobronchial tumors adjacent to internal organs that might be damaged by intensive external beam radiation, but are easily accessed with a flexible bronchoscope. This treatment is mostly palliative. 30 patients underwent such palliative high-dose endobronchial brachytherapy to alleviate malignant airway obstruction. With the aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted adjacent to the tumor and treatment delivered using a 192Ir remote afterloader for 5-10 min, in 2 or 3 sessions. There was symptomatic improvement in 26 (86%) and objective improvement in 27 (90%). 1 patient died of hemoptysis.

Aged↗
PubMed2000

Molecular imprinting of bulk, microporous silica

Molecular imprinting aims to create solid materials containing chemical functionalities that are spatially organized by covalent or non-covalent interactions with imprint (or template) molecules during the synthesis process. Subsequent removal of the imprint molecules leaves behind designed sites for the recognition of small molecules, making the material ideally suited for applications such as separations, chemical sensing and catalysis. Until now, the molecular imprinting of bulk polymers and polymer and silica surfaces has been reported, but the extension of these methods to a wider range of materials remains problematic. For example, the formation of substrate-specific cavities within bulk silica, while conceptually straightforward, has been difficult to accomplish experimentally. Here we describe the imprinting of bulk amorphous silicas with single aromatic rings carrying up to three 3-aminopropyltriethoxysilane side groups; this generates and occupies microporosity and attaches functional organic groups to the pore walls in a controlled fashion. The triethoxysilane part of the molecules' side groups is incorporated into the silica framework during sol-gel synthesis, and subsequent removal of the aromatic core creates a cavity with spatially organized aminopropyl groups covalently anchored to the pore walls. We find that the imprinted silicas act as shape-selective base catalysts. Our strategy can be extended to imprint other functional groups, which should give access to a wide range of functionalized materials.

Journal Article↗
PubMed2000

Cloning and expression, pharmacological characterization, and internalization kinetics of the pituitary GnRH receptor in a metatherian species of mammal.

Gonadotropin-releasing hormone receptors (GnRH-Rs) expressed in the pituitary of eutherian species of mammal are unique in lacking the cytoplasmic C-terminal tail characteristic of GnRH-Rs of nonmammalian vertebrates and other G protein-coupled receptors. To further investigate evolutionary relationships among vertebrate GnRH-Rs, a full-coding region cDNA of the pituitary GnRH-R was cloned from a metatherian marsupial mammal, the Australian brushtail possum (Trichosurus vulpecula). We have determined the pharmacological characteristics and internalization kinetics of this GnRH-R from an early evolved, metatherian species of mammal and compared it with the corresponding receptors in eutherian species of mammal and nonmammalian vertebrates. The predicted GnRH-R protein from the possum pituitary has high homology with the other mammalian GnRH-Rs (80% identity) and, in common with other mammals, lacks an intracellular C-terminal tail. The ligand selectivity of the possum GnRH-R transfected into COS-1 cells, assessed using inositol phosphate assays and radioreceptor binding assays, was similar to that of the other mammalian GnRH-Rs, and distinct from those of the nonmammalian GnRH-Rs. The pharmacological characteristics of the possum GnRH-R were similar to those of other mammalian GnRH-Rs, for a selection of agonists (including naturally occurring GnRH ligands and superagonists) and antagonists. Receptor-mediated internalization of GnRH agonist by the possum GnRH-R was slightly more rapid than that of the human GnRH-R, while the internalization kinetics of the chicken GnRH-R, in which a cytoplasmic C-terminal tail is present, was considerably more rapid. In terms of the evolution of the GnRH-R in vertebrates, the possum (a metatherian mammal) GnRH-R has a striking resemblance, in both structure and pharmacological characteristics, to GnRH-Rs in eutherian mammals, which are quite distinct from the nonmammalian vertebrate GnRH-Rs, and are unique among G protein-coupled receptors in lacking an intracellular C-terminal tail. The distinct structure of the pituitary GnRH-R in mammalian vertebrates is likely to have important functional consequences in the reproductive physiology of mammals.

Amino Acid Sequence↗
PubMed2000

Improved growth velocity with intensive dialysis. Consequence or coincidence?

Growth failure in children with end-stage renal disease remains a difficult problem. A 2.5-month-old baby in renal failure due to primary hyperoxaluria type I received intensive dialysis aimed at decreasing oxalate tissue accretion. Over 5.5 months, while awaiting transplantation, his growth velocity was 29 cm/year compared with an average 4 cm/year in infants on hemodialysis and 22 cm/year in normal infants of this age. This remarkable growth rate, which could have represented catch-up growth, is hypothesized to be related to the delivered dialysis dose. It is suggested that this relationship be evaluated in a prospective randomized trial.

Growth↗
PubMed2000

Effect of creatine feeding on maximal exercise performance in vegetarians.

The effect of creatine supplementation on exercise performance in vegetarians was examined. Creatine was ingested for 1 week by a group of vegetarians (VC) and meat-eaters (MC); a control group of meat-eaters was fed only glucose (MG). Exercise performance during three, 20-s maximal cycling tests (modified Wingate anaerobic test, WAnT) was determined before and after creatine supplementation. Blood samples were also drawn before and after exercise prior to and after supplementation. Basal plasma creatine (after an overnight fast) averaged (SE) 11 (2) microM in VC, and 24 (2) and 23 (7) microM in MG and MC, respectively (P < 0.05 for VC vs meat-eaters). These findings were expected, since most of the body's exogenous creatine source is meat. There was no significant difference in any other parameter between groups prior to supplementation. Creatine feedings significantly increased body mass (approximately 1 kg) and mean power output during the WAnTs (approximately 5%) to a similar extent in the VC and MC groups (P < 0.05-0.001). These parameters were not affected by supplementation in the MG group. Peak power output was also significantly increased by supplementation in MC (approximately 5%, P < 0.05), but not in VC. It is concluded that vegetarians and meat-eaters respond to creatine feedings with similar increases in mean power output during short-term, maximal exercise.

Adult↗
PubMed2000

Chromosomal localization, genomic characterization, and mapping to the Noonan syndrome critical region of the human Deltex (DTX1) gene.

The human Deltex (DTX1) gene encodes a cytoplasmic protein that functions as a positive regulator of the Notch signaling pathway. We have determined the genomic organization and map location of the human gene. DTX1 encodes a 2.5-kb cDNA that is composed of nine exons. The DTX1 gene maps to chromosomal region 12q24 in the vicinity of the Noonan syndrome critical region. We have fine-mapped DTX1 to within this critical region and evaluate it as a candidate gene for this disorder.

Carrier Proteins↗