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Biomedical subjects

R Katz

Publications and source records attributed to R Katz.

At least 109 records · Page 6Linked to original sources

Radiosensitivity parameters for lethal mutagenesis in Caenorhabditis elegans.

For the first time track structure theory has been applied to radiobiological effects in a living organism. Data for lethal mutagenesis in Caenorhabditis elegans, obtained after irradiation with nine different types of ions of atomic number 1-57 and gamma rays have yielded radiosensitivity parameters (E0, sigma 0, kappa, m = 68 Gy, 2.5 x 10(-9) cm2, 750, 2) comparable with those found for the transformation of C3HT10 1/2 cells (180 Gy, 1.15 x 10(-10) cm2, 750, 2) but remote from those (E0 and sigma 0 = approximately 2 Gy, approximately 5 x 10(-7) cm2) for mammalian cell survival.

Animals↗

[Long term follow-up of patients with chronic hepatitis due to hepatitis C virus].

Thirty two patients (18 males whose ages ranged from 32 to 68 years old) with hepatitis C virus chronic hepatitis (positive anti-HCV by ELISA, confirmed by RIBA II) that were followed by the authors during 2 to 25 years, were retrospectively analyzed. Thirteen subjects had a history of blood transfusions, one had an accidental pinprick and other a sexual contact with a HCV positive individual; the transmission source was not identified in the resting 19 subjects. Only five individuals had an acute onset. The rest of the patients had few symptoms with moderate and fluctuating transaminase elevations. Liver biopsy at the onset showed a chronic hepatitis with moderate activity, even in 15 individuals with cirrhosis (47%). During follow up, six subjects deteriorated clinically, appearing liver failure and three of these died 4, 5 and 14 years after the disease appearance. No subject developed a hepatocarcinoma.

Adult↗

Survey of cellular radiosensitivity parameters.

A model of the formation of particle tracks in emulsion has been extended through the use of biological target theory to formulate a theory of the response of biological cells and molecules of biological importance to irradiation with energetic heavy ions. For this purpose the response to gamma rays is represented by the single-hit, multitarget model with parameters m and D0, while additional parameters kappa (or a0) and sigma 0 are required to represent the size of internal cellular targets and the effective cross-sectional area of the cell nucleus, respectively, for heavy-ion bombardments. For one-or-more-hit detectors, only the first three of these parameters are required and m = 1. For cells m is typically 2 or more. The model is developed from the concept that response to secondary electrons follows the same functional form for gamma rays and for the gamma rays surrounding an ion's path. Originally applied to dry enzymes and viruses in 1967, the model of the one-hit detector has been extended to emulsions, to other physical and chemical detectors, to single- and double-strand breaks in DNA in EO buffer and to three E. coli strains. The two-hit response has been observed for "track core" effects in radiation chemistry, for supralinearity in thermoluminescent dosimeters and for desensitized nuclear emulsions, where hit numbers up to 6 have been observed. In its extension to biological cells, additional concepts are required relating to the character of the track, namely the grain-count and track-width regimes, and to the ability of multitarget systems to acquire damage from intertrack delta rays (called gamma kill) as well as from intratrack delta rays (called ion kill). The model has been applied to some 40 sets of radiobiological data obtained from gamma, track-segment heavy-ion and neutron irradiations. Here we elaborate on the meaning of these concepts, tabulate the cellular parameters, and display their systematic behavior and the relationships among them. In particular the parameter kappa, which serves to determine the location in Z*2/beta 2 of the maximum value of the RBE, shows little variation among cell types, while D0, which describes the response to gamma rays and sigma 0, which appears to indicate the target size, varies over many orders of magnitude.

Animals↗

Dose.

The universal use of dose as a normalizing parameter in radiobiology is based entirely on the availability of measuring instruments. It is a poor basis for predicting or understanding the relationship between an irradiation and the resulting end point. Energy deposited is not the cause of an interaction. It is a secondary effect. The interaction is best described by fluence and cross section. Energy deposited depends principally upon inelastic collision cross sections for the interaction of electrons with molecules. Especially for heavy-ion bombardments, for high-LET radiations, inelastic electron collision cross sections relate only remotely to the observed end points of interest. When dose is used to describe effects observed with radiations of different "quality," response predictions can be very wide of the mark. One way to describe such a relationship is through the relative biological effectiveness (RBE). If we consider the RBE to be a correction factor to be applied to a prediction of response based on dose, we find that its values range from 0.01 to infinity. It is apparent that in general dose is a useless predictor of response, except in narrowly defined circumstances.

Animals↗

Bowen's disease of the nail bed and periungual area. A clinicopathologic analysis of seven cases.

BACKGROUND: This article describes the clinical and histologic features of seven cases of Bowen's disease (BD) of the nail bed, evaluates the role of human papillomavirus in the bowenoid change, and discusses optimal therapy. OBSERVATION: The patients presented with the clinical features of verruca vulgaris (n = 3), nail dystrophy and onycholysis (n = 2), paronychia (n = 1), and acral melanoma (n = 1). Histologically, the lesions demonstrated acanthosis, hyperkeratosis, and anaplasia, involving the full thickness of the epithelium. In four cases, human papillomavirus type 16 was demonstrated by in situ hybridization. Six lesions were treated by Mohs micrographic surgery, and one case was treated with topical 5% fluorouracil. In two cases, lesions recurred 1 and 2 years following surgery. In the case treated with topical 5% fluorouracil, residual BD was found 6 weeks after therapy. This case was then treated by Mohs surgery. CONCLUSIONS: Bowen's disease of the nail bed and periungual area may present clinically as various inflammatory and neoplastic conditions. An important clinical finding in differentiating BD of the nail bed from verruca is the presence of scaling and onycholysis that are out of proportion to the verrucous changes. Human papillomavirus type 16 may be etiologically related to BD of the nail bed and periungual area. Mohs micrographic surgery is recommended for adequate excision and maximal preservation of normal tissue and function.

Adult↗

Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.

OBJECTIVES: To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy. DESIGN: A randomized, double-blind, multicenter, placebo-controlled trial. SETTING: Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices. PATIENTS: Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial. INTERVENTIONS: Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks. MAIN OUTCOME MEASURES: The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure. RESULTS: By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively. CONCLUSION: Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.

Adult↗

Distinct patterns of spatial frequency response by normal, recovered optic neuritis, and normal fellow eyes to a new linearly variable neutral density device.

Upon apparent recovery from optic neuropathy, structural damage to the optic nerve may remain while usual measures of visual function appear normal. To test for such damage, the logarithm of optical density to cause a pattern to disappear is read directly on the scale of our device. Patients in the first study observed the disappearance of a red Amsler grid; this Threshold Amsler Score, used jointly with acuity scores, separates normal eyes from eyes with optic neuropathies. Patients in the second study used the device to measure the disappearance of the highest contrast Vistech patterns to show that this device, used over a range of spatial frequencies, differentiates "subclinical" neuropathies (recovered optic neuritis eye; never symptomatic fellow eye to a diagnosed eye) from normal eyes. This device may measure the functional photopic brightness of the stimulus pattern; when the score from our device is higher, the range of photopic brightness for the stimulus is wider, and the retina is more sensitive to contrast.

Adolescent↗

A rational approach to the use of fine-needle aspiration biopsy in the evaluation of primary and recurrent neoplasms in children.

Fine-needle aspiration (FNA) has been recommended as a technique for accurate evaluation and diagnosis of childhood malignancies. Very little data exist regarding the limitations and utility of FNA in children. We reviewed our experience over the past 5 years to assess the clinical use of FNA and its limitations. One hundred seventy-three FNAs were performed in 156 patients who ranged in age from 7 months to 18 years. Sixty-three patients were female and 110 were male. Thirty-seven aspirations were obtained to evaluate new masses in children with previously diagnosed malignancies. FNA allowed diagnosis of the malignancy in 90% of patients with solid tumors, whereas only 9 of 19 patients with lymphomas were diagnosed accurately with FNA. The specificity was 99.7%. Inadequate material was obtained in 13 aspirates. Insufficient material was obtained in 14% of patients who had FNA as their initial diagnostic tool. Four false-negatives were obtained while evaluating children for recurrent disease. There were 16 true-negative biopsies. These data suggest that FNA is an excellent tool for diagnosing both recurrent malignancies as well as previously undiagnosed solid tumors in the pediatric population but is inadequate to diagnose children with suspected undiagnosed lymphomas. Negative studies should be considered nondiagnostic and followed by open biopsies when clinical suspicion of malignancy is high.

Adolescent↗

Pharmacokinetics of continuous infusions of fentanyl in critically ill children.

OBJECTIVE: To determine the pharmacokinetics of fentanyl when used as a long-term continuous infusion for sedation/analgesia in mechanically ventilated critically ill infants and children. DESIGN: Prospective, case series. SETTING: A university hospital pediatric intensive care unit (ICU). PATIENTS: Nineteen mechanically ventilated infants and children (0.05 to 14 yrs of age) who received continuous infusions of fentanyl for > 24 hrs. INTERVENTIONS: None. MEASUREMENTS: Plasma concentrations of fentanyl were measured 1 hr after a loading dose and at various intervals during and after the infusions were discontinued. Noncompartmental pharmacokinetic variables, total body clearance, volume of distribution at steady state, and terminal elimination half-life were calculated. Clinical sedation scores, ventilatory settings, pupillary size and reactivity, and patient demographics were recorded. RESULTS: After the use of fentanyl by long-term infusion, the volume of distribution at steady state was increased 15.2 L/kg (range 5.1 to 30.5) and the terminal elimination half-life was prolonged 21.1 hrs (range 11.2 to 36.0) compared with previous studies. Clearance was rapid and consistent with other studies. There was a large interpatient variability in clearance that was age dependent. Clearance did not appear to increase over time. CONCLUSIONS: Total body clearance of fentanyl is highly variable and it should be dosed to effect. Patients seen in a pediatric ICU may require a ten-fold variability in fentanyl infusion rates to achieve similar levels of sedation.

Adolescent↗

Distribution of recurrent inhibition in the human upper limb.

The distribution of homonymous and heteronymous recurrent inhibition among the motor nuclei innervating the main muscles of the human upper limb has been investigated in 25 healthy subjects. Homonymous recurrent inhibition was studied with a specially designed electrophysiological method with paired H-reflexes, previously described by Bussel & Pierrot-Deseilligny (1977), combined with a pharmacological study using a cholinergic agonist, the L-acetylcarnitine (Rossi & Mazzocchio 1991). These methods were used to investigate the Flexor Carpi Radialis (FCR), Extensor Carpi Radialis (ECR), Opponens Pollicis (OP) and Abductor Digiti Minimi (ADM) motor nuclei. In the Deltoid, Triceps, Flexor Carpi Ulnaris (FCU) and Extensor Carpi Ulnaris (ECU) motor nuclei in which it was impossible to evoke clearly distinguishable H-reflexes, homonymous recurrent inhibition was studied with the PSTH technique: homonymous recurrent inhibition was found in Deltoid, Triceps, FCR, FCU, ECR, ECU motor nuclei but not in OP and ADM motor nuclei. Heteronymous recurrent inhibition was studied with the PSTH technique in the Deltoid, Biceps, Triceps, FCR, ECR, FCU, ECU, Flexor Digitorum Communis (FDC), Extensor Digitorum Communis (EDC) motor nuclei as well as those innervating the intrinsic muscles of the hand. The following results were obtained: (1) motor neurones innervating muscles acting at digits do not receive any heteronymous recurrent inhibition; (2) motor neurones innervating muscles acting at the wrist give recurrent inhibition to motor nuclei of proximal muscles but do not receive any recurrent projections from the latter; and (3) motor neurones innervating proximal muscles (acting at shoulder or elbow) are interconnected by recurrent inhibition and receive heteronymous recurrent projections from some wrist muscles but not from intrinsic hand muscles.

Adult↗

Experimental and theoretical cross sections for Escherichia coli mutants B, B/r, and Bs-1 after heavy-ion irradiation.

Data for the inactivation of three Escherichia coli mutants by energetic heavy ions are fitted by the track theory of a one-hit detector in an extended target mode. The respective E0's are 46, 36.5, and 12.6 Gy for E. coli B, B/r, and Bs-1 and a0, the assumed target radius, is 0.5 microns for all three. The parameter E0, the D37 with gamma rays, is measured directly, while a0 is fitted to the data. It is significant that neither a point target model nor calculations with a0 = 0.2 and 1.0 micron fit the data. Our fitted target radius, a0, approximates the size of the bacterium. These results raise questions as to why the E. coli mutants are one-hit detectors, and concerning the differences in the E0's in relation to a mechanistic interpretation of cell killing.

Acceleration↗

Validity and reproducibility of multi-test skin test device.

Thirty patients were skin tested by Multi-Test and Morrow Brown needle using antigens, histamine, glycerosaline, and blank controls to examine reproducibility and influence of positive reactions on adjacent negative controls. There was no evidence that histamine or strongly positive antigen reactions affected adjacent negative controls. Multi-Test was more reproducible, and preferred by patients over Morrow Brown.

Adolescent↗

Relative effectiveness of mixed radiation fields.

For all one-hit detectors the relative effectiveness of a mixed radiation field may be found as the dose-weighted average of the relative effectiveness of its components, segregated according to the atomic number Z and the energy T. We emphasize that this procedure is incorrect for mammalian cells, whatever the nature of the segregation.

Radiation Effects↗