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Biomedical subjects

S Grossman

Publications and source records attributed to S Grossman.

At least 37 records · Page 2Linked to original sources

Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy.

CONTEXT: Indications are not well defined for follow-up colonoscopy for all patients with distal colonic tubular adenomas (TAs) found at screening sigmoidoscopy. OBJECTIVE: To determine whether distal adenoma size, number, and villous histology, along with family history and age, are predictors of advanced proximal colonic neoplasia. DESIGN: Cross-sectional analysis conducted between January 1, 1994, and December 31, 1995. SETTING: Large group-model health maintenance organization in northern California. PATIENTS: A total of 2972 asymptomatic subjects aged 50 years or older undergoing colonoscopy as follow-up to a screening sigmoidoscopy. MAIN OUTCOME MEASURE: Based on sigmoidoscopy, colonoscopy, and pathology reports, occurrence of advanced proximal neoplasia, defined as adenocarcinoma or TAs 1 cm or larger or with villous features or severe dysplasia located beyond sigmoidoscopic view. RESULTS: The prevalence of advanced proximal neoplasia was similar among patients with no TAs at sigmoidoscopy, those with TAs less than 1 cm in diameter, and those with TAs 1 cm in diameter or larger (prevalence, 5.3%, 5.5%, and 5.6%, respectively). Of patients with a distal tubulovillous or villous adenoma, 12.1% had advanced proximal neoplasia. In multivariate analyses, having a distal tubulovillous adenoma or villous adenoma was the strongest predictor of advanced proximal neoplasia (odds ratio, 2.30; 95% confidence interval, 1.69-3.14). Age of 65 years or older, having more than 1 adenoma, and a positive family history of colorectal cancer were also significant predictors. Distal adenoma size was not a significant predictor in any multivariate analyses. CONCLUSIONS: Advanced proximal neoplasia is not uncommon in subjects with or without distal TAs, but subjects with advanced distal histology and those older than 65 years are at increased risk. Age-specific screening using sigmoidoscopy starting at ages 50 to 55 years and colonoscopy after age 65 years may be justified.

Adenocarcinoma↗

Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.

BACKGROUND: This study examined changes in attention-deficit hyperactivity (ADHD) behaviors and motor and vocal tics during long-term treatment with methylphenidate. METHODS: Thirty-four prepubertal children with ADHD and chronic multiple tic disorder (who had participated in an 8-week, double-blind, placebo-controlled methylphenidate evaluation) were evaluated at 6-month intervals for 2 years as part of a prospective, nonblind, follow-up study. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and physician. Videotapes of the simulated classroom were scored by coders who were blind to treatment status. RESULTS: There was no evidence (group data) that motor tics or vocal tics changed in frequency or severity during maintenance therapy compared with diagnostic or initial double-blind placebo evaluations. Behavioral improvements demonstrated during the acute drug trial were maintained during follow-up. There was no evidence (group data) of clinically significant adverse drug effects on cardiovascular function or growth at the end of 2 years of treatment. CONCLUSIONS: Long-term treatment with methylphenidate seems to be safe and effective for the management of ADHD behaviors in many (but not necessarily all) children with mild to moderate tic disorder. Nevertheless, careful clinical monitoring is mandatory to rule out the possibility of drug-induced tic exacerbation in individual patients.

Attention Deficit Disorder with Hyperactivity↗

Lipopolysaccharide-induced oxidative stress in the liver: comparison between rat and rabbit.

In the present study the effect of LPS on biochemical systems involved in radical formation and scavenging processes in tissues from rabbit (LPS-sensitive) and rat (LPS-resistant) was investigated. The results obtained show a significant enhancement in the endogenous antioxidative enzyme system in rats as a result of LPS injection. In rats, 24 h after LPS injection, glutathione peroxidase (G-POX) and superoxide dismutase (SOD) activities were increased by 60% and 120%, respectively, compared to the control. However, in rabbits the increase in these activities was relatively mild. Moreover, NADPH-oxidase activity, which produces superoxide radical, was increased about twofold in rabbit, 15 h following LPS injection. In rats, injection of LPS did not result in any significant changes in the activity of this enzyme. In rats, a decrease in malonaldehyde (MDA) levels appeared after injection of LPS, while in contradistinction, the peroxidative levels of lipids in the rabbit's liver were increased about 3-fold. Injection of D-galactosamine (Gal-N) in combination with LPS significantly increased the sensitivity of rats to LPS characterized by a significant increase in NADPH-oxidase activity. This study indicates that one possible mechanism (among others) that may explain the relative sensitivity of rabbits compared to rat, may be related to the increase in the production of reactive oxygen substances (ROS) which is not accompanied by a concomitant increase of the protective antioxidative enzymes. Furthermore, the relative resistance of the rat was found to be related to an increase in the activity of the protective antioxidative systems following administration of LPS.

Animals↗

Integrating multidimensional stress management into a baccalaureate nursing curriculum.

The mandate for self-care for holistic nurses can be satisfied with a multidimensional stress management program. This article describes a quasiexperimental pilot study that assessed the need for such a program for senior students in a baccalaureate degree nursing program. Strategies are suggested to integrate these techniques into nursing education.

Adaptation, Psychological↗

Practical implementation of a modified continual reassessment method for dose-finding trials.

PURPOSE: We describe a practical, reliable, efficient dose-finding design for cytotoxic drugs applied in a multi-institutional setting. METHODS: The continual reassessment method (CRM) was modified for use in phase I trials conducted through the New Approaches to Brain Tumor Therapy (NABTT) Consortium. Our implementation of the CRM uses (1) a simple dose-toxicity model to guide data interpolation, (2) groups of three patients to minimize calculations and stabilize estimates, (3) investigators' clinical knowledge or opinion in the form of data to make the process easier to understand, and (4) a flexible computer program and interface to facilitate calculations. RESULTS: The modified CRM was used in two dose-finding trials of 9-aminocamptothecin in patients with newly diagnosed and recurrent glioblastoma who were taking anticonvulsant medication. The CRM located the maximum tolerated dose (MTD) efficiently in both trials. Compared to conventional designs, the CRM required slightly more than half the number of patients expected, did not greatly overshoot the MTD (i.e. no patients were treated at dangerously high doses), and did not underestimate the MTD. CONCLUSIONS: Our experience demonstrates the feasibility of implementing this design in multi-institutional trials and the possibility of performing dose-finding studies that require fewer patients than conventional methods.

Antineoplastic Agents↗

Role-modeling experience improves nursing students' attitudes toward people living with AIDS.

Two groups of student nurses were given on AIDS Knowledge/Attitudes survey before different clinical experiences. Group One worked with nurses experienced in the care of persons living with AIDS (PLWA) on a high-acuity unit with many AIDS patients. The other group were precepted on a acute-care unit with no AIDS patients. Outcomes measures revealed significantly better student attitude scores for Group One on scales measuring (1) avoidance intentions to working with PLWA and (2) attitude toward homosexuals.

Acquired Immunodeficiency Syndrome↗

Short course radiotherapy is an appropriate option for most malignant glioma patients.

PURPOSE: To determine whether a shortened course of radiotherapy (RT) is an appropriate treatment option for malignant glioma patients. METHODS AND MATERIALS: Prognostic groups published by the Radiation Therapy Oncology Group (RTOG) are used to compare results for a short radiotherapy regimen with results of aggressive protocol treatment. The study group includes 219 patients treated during 1975-1993 with 51 Gy in 17 fractions. Patients were retrospectively assigned to six prognostic groups previously identified in a recursive partitioning analysis of the RTOG. The prognostic groups are based on age, histology, performance status, mental status, neurologic function, resection extent, length of symptoms, and RT dose. RESULTS: The six RTOG prognostic groupings were significantly predictive of outcome for patients treated with this shortened regimen (log-rank, p < 0.001). The median survival for our patients by RTOG groups 1-6 were 68, 57, 22, 13, 8, and 5 months, respectively. Two-year survival results were 64, 67, 45, 8, 3, and 3%. The median and two-year survival results for each prognostic grouping were similar to the results achieved by aggressive treatment on RTOG malignant glioma trials for selected patients. Treatment toxicity was uncommon. CONCLUSION: This shortened regimen is an appropriate treatment option for most malignant glioma patients (RTOG groups 4-6), resulting in similar survival as standard regimens with reduced patient effort and cost. Although acute side effects are acceptable and the risk of brain necrosis is low, we do not recommend this treatment to the minority of patients who have a substantial long term survival probability (RTOG groups 1-3) because long term neurocognitive assessment is lacking.

Brain Neoplasms↗

Cellular inflammatory responses during immediate, developing, and established late-phase allergic cutaneous reactions: effects of cetirizine.

BACKGROUND: In some previous studies, the antihistamine cetirizine has inhibited both developing (at 6 hours) and established (at 24 hours) gross late-phase skin reactions (LPR) to pollen antigens, possibly relevant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. OBJECTIVE: To characterize cetirizine effects on gross and histologic inflammatory events from 20 minutes to 24 hours after intradermal antigen challenge in sensitive patients. METHODS: Gross and histologic responses to intradermal pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accumulated neutrophils, eosinophils, activated (EG2+) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (ECP) from eosinophils were also assessed. RESULTS: During placebo treatment, wheal-and-flare responses were significantly greater to antigen at 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antigen challenge sites than at buffer diluent sites. During cetirizine treatment, these wheal-and-flare responses to antigen were inhibited significantly (p < 0.01) but gross LPRs were not affected. During placebo treatment, significantly more cells per high-power field were found in antigen sites than in buffer sites of neutrophils at 20 minutes (p < 0.01) and 24 hours; than in eosinophils at 20 minutes, 6 hours, and 24 hours (p < 0.01 for each); than in EG2+ cells at 20 minutes (p = 0.004), 6 hours (p = 0.001), and 24 hours (p = 0.02); and at T lymphocyte sites at 24 hours (p = 0.001). Extracellular deposition of lactoferrin and ECP was significantly greater at antigen sites than at buffer sites at 6 and 24 hours. Cetirizine treatment had no significant effect on these responses. CONCLUSION: Neutrophils, eosinophils, and T lymphocytes were persistently more common at antigen sites than at buffer sites through 24 hours. Many of these neutrophils and eosinophils were activated, releasing more lactoferrin and ECP into the extracellular dermis for at least 24 hours after antigen challenge. Cetirizine inhibited gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.

Administration, Cutaneous↗

The Colon Cancer Prevention Program (CoCaP): rationale, implementation, and preliminary results.

Although there is now solid evidence to support the efficacy of colorectal cancer screening, few health care systems have developed comprehensive screening programs. This report describes the scientific rationale, development and implementation strategies, and preliminary results of the Colon Cancer Prevention Program (CoCaP) of the Northern California Region of the Kaiser Permanente Medical Care Program. CoCaP is a sigmoidoscopy-based screening program that aims to provide screening to all average-risk program members once every 10 years beginning at age 50. During the first 2 years of the program, more than 100,000 sigmoidoscopies were performed in age-eligible members (age 50 years and above). Seventy-five percent of these were screening examinations. Participating endoscopists include gastroenterologists, generalist physicians, and a growing number of non-physicians, primarily nurses, nurse-practitioners or physicians' assistants. Data on depth of insertion and polyp yield suggest that non-physicians quickly become as proficient as physician endoscopists. The long-term goals of the CoCaP program are to reduce the incidence of and mortality from colorectal cancer. Collection and analysis of data from the screening examinations and follow-up colonoscopies will enable CoCaP to refine its screening algorithm and to quantify program effectiveness.

Algorithms↗

The effect of retinol and retinoic acids on lipoxygenase activity.

Lipoxygenase catalyzes the dioxygenation of polyenoic fatty acids such as linoleate and arachidonate. The aim of the present study was to examine the effect of retinol, all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid. Lipoxygenase activity toward linoleic acid was followed by determining changes in absorption at 234 nm. All retinoids inhibited lipoxygenase-1 and lipoxygenase-2 activity. Lipoxygenase-2 activity towards linoleic acid was rapid at pH 6.5; all-trans-retinol (10 microM) caused a 50% inhibition in reaction rate. All-trans-retinol was oxidized in parallel with diene production by lipoxygenase-2. Lipoxygenase-2 activity on linoleic acid was competitively inhibited by all-trans-retinol and all-trans-retinoic acid; 13-cis-retinoic acid exhibited mixed type inhibition. Activity of lipoxygenase-1 towards linoleic acid at pH 9.0 was also inhibited by retinoic acids by 32-73%. All-trans-retinoic acid and 13-cis-retinoic acid inhibited lipoxygenase-1 activity competitively, whereas all-trans-retinol inhibited lipoxygenase-1 activity in a mixed manner. These findings suggest that retinoids may bind to the active site of the enzyme or simultaneously act as an antioxidant.

Binding Sites↗

Clozapine and haloperidol modulate N-methyl-D-aspartate- and non-N-methyl-D-aspartate receptor-mediated neurotransmission in rat prefrontal cortical neurons in vitro.

The effects of the antipsychotic drugs haloperidol and clozapine on N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated neurotransmission were examined and compared in pyramidal cells of the medial prefrontal cortex in rat brain slices by using the techniques of intracellular recording and single-electrode voltage-clamp. The bath administration of either haloperidol or clozapine produced a marked facilitation (300-400%) of NMDA-evoked responses in a concentration-dependent manner. The EC50 values of haloperidol and clozapine were 38 and 14 nM, respectively. At concentrations of > or =100 nM, clozapine, but not haloperidol, produced bursts of excitatory postsynaptic potentials (EPSPs), which were blocked by glutamate receptor antagonists, suggesting that these EPSPs were the result of increasing release of excitatory amino acids. Haloperidol, but not clozapine, produced a concentration-dependent inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced current with an EC50 value of 37 nM. Haloperidol significantly decreased the amplitude of EPSPs evoked by the electrical stimulation of the forceps minor, whereas clozapine increased the amplitude of these EPSPs. The study of current-voltage relationship indicates that clozapine preferentially potentiates NMDA receptor-mediated transmission, whereas haloperidol depresses the non-NMDA receptor-mediated response, which probably obscures its potentiating effect on NMDA receptor-mediated EPSPs.

Action Potentials↗

How can nurses use limit setting to facilitate spinal cord patients' independence?

Learning limit setting techniques is necessary for the entire team in order to have consistent positive patient outcomes. Team building exercises will assist in supporting restructuring of acute care units' healthcare delivery. Difficult patients need to participate in their plan of care along with representatives from each discipline. Caregiver competency in psychological, physical, technical, and physiological aspects of care for the SCI patient facilitates patient independence. This is a result of our increased knowledge which teaches us that these kind of patients can be more independent and, hence more in control, than caregivers may realize. Patients will be less likely to be manipulative and abusive to the healthcare staff if they feel more in control of their care and their lives.

Activities of Daily Living↗

In vitro and in vivo effects of beta-carotene on rat epidermal lipoxygenases.

The in vitro and in vivo interaction between beta-carotene (BC) and lipoxygenase (LOX) was studied in rat skin. Significant in vitro inhibitory effects of BC on epidermal LOX activity were observed with both linoleic acid or arachidonic acid as substrate. Lineweaver-Burk plots for the inhibition of epidermal purified LOX indicated mixed competitive/non-competitive inhibition. In vivo effects of BC were examined in an ultraviolet A (UVA) irradiation model. Following UVA irradiation (200 Kjoule/m2) significant increases in LOX activity and malondialdehyde (MDA) values were found, whereas catalase activity was significantly decreased. Topical pretreatment of skin with BC prevented increases in LOX activity and MDA values 4 hr post-irradiation. Catalase activity was not affected by BC treatment. BC was more effective at preventing UVA induced lipid peroxidation at low then at high concentrations. Our present results indicate the protective potential of BC on in vivo UVA induced skin damage by reduction of non-enzymatic and enzymatic lipid peroxidation.

Animals↗

Lipoxygenase activity in heart cells.

Arachidonic acid (AA) metabolism via the lipoxygenase (LOX) pathway in rat hearts and in cultured rat cardiomyocytes was investigated using 1-[14C]AA. LOX activity was detected in the microsomal fraction, in the high speed supernatant prepared from rat hearts and in rat cardiomyocyte supernatant. LOX products from all fractions comigrated in thin layer chromatography as 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE. Enzyme linked immunosorbent assay for 12-HETE showed its formation by the microsomal fraction, the ammonium sulfate (AS) pellet, and by rat cardiomyocyte supernatant, while radioimmunoassay for 15-HETE showed its formation only by the AS pellet. The properties of LOX in each fraction are reported here.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha.

The transcription factor ISGF3 transduces interferon (IFN)-alpha signals and activates the transcription of cellular antiviral defence genes. Adenovirus E1A blocks the IFN-alpha response, allowing unhindered viral replication. ISGF3 consists of Stat1, Stat2 and p48. Here we show that p300 and/or CBP (CREB-binding protein), which are transcription adaptors targeted by E1A, interact specifically with Stat2. Binding occurs between the first cysteine-histidine-rich region of p300/CBP and the carboxy-terminal segment of Stat2, a domain essential for ISGF3 function. We find that this domain of Stat2 has transactivation potential, which correlates with its binding to p300/CBP. Moreover, E1A represses Stat2 transactivation and IFN-alpha-activated transcription by inhibiting p300/CBP function. This provides a new mechanism for inhibition of the IFN-alpha-activated antiviral response by E1A, and supports the view that E1A binding to p300/CBP has functional significance for adenovirus replication in its natural host.

Adenoviridae↗

Interaction between beta-carotene and lipoxygenase in human skin.

beta-Carotene is widely used in skin care therapy. Its effects on skin are unclear, but actions on lipid peroxidation pathways may be an important element of any protection activities it exerts. This study examines the possible effects of Beta-carotene on enzymatic lipid peroxidation by lipoxygenase in human skin, using in vitro and ex vivo models. The effect of Beta-carotene on lipid peroxidation in human skin were studied in skin homogenates and in a semi-in vivo model of skin penetration, using [1-14C]-arachidonic acid or [1-14C]-linoleic acid as substrate. When relatively low concentrations (about 0.3 microM) of beta-carotene were added to epidermal homogenates, the major metabolites of arachidonic acid (12-hydroxy-cis-5,8,14, trans-10-eicosatetraenoic acid and 15-hydroxy-cis-5,8,11, trans-13-eicosatetraenoic acid) and of linoleic acid (13-hydroxy-cis-9, trans-11-octadeca dienoic acid and 9-hydroxy-trans-10, cis-12-octadeca dienoic acid) were significantly decreased. Following [1-14C]-linoleic acid penetration through the semi in vivo model layers, the skin surface was the main site in which the major linoleate product, 13-hydroxy-cis-9, trans-11-octadeca dienoic acid was detected. Furthermore, its level was inhibited by up to 80%, compared with the control, when beta-carotene was added to the system. The data presented in this study suggest possible interactions between beta-carotene and human epidermal lipoxygenase. Beta-carotene may effect lipid peroxidation in human skin, either as a free radical scavenger or as a specific lipoxygenase inhibitor.

Antioxidants↗

National Hockey League players from North America are more violent than those from Europe.

It is commonly believed by hockey fans that European hockey players rely more on skill while. North American players are more violent. The number of penalty minutes gathered by European and North American players in the National Hockey League's 1995-1996 season was examined. When corrected for the low proportion of European players, North American players had significantly more penalty minutes than European players.

Aggression↗

Definition and management of anxiety, agitation, and confusion in ICUs.

Critically ill patients require continuous assessment of their need for sedation and pain management. The purpose of this study was to develop a consistent categorization of patient's symptoms and to identify actions that yield effective patient outcomes. Nurses in this study described patients with sedation problems as those who were disoriented or aggressively acting out, fearful and restless, or manifesting changes in orientation, memory loss, or mental status. Twenty-seven medical intensive care unit (MICU) nurses volunteered to complete a questionnaire about their assessment process in determining patient's sedation needs, interventions, and evaluation criteria for patient outcomes. Fifty-five patient questionnaires were completed by the nurses. Nurses identified separate subjective and objective cues for patients' anxiety, agitation, and confusion. The most frequently identified nursing actions were assessment to differentiate between pain, anxiety, agitation, and confusion; personal reassurances, relaxation and other physical comfort techniques; administer prescribed medication; collaborate with a physician to identify cause; and give additional prescribed medication. Effective outcome measures included stable vital signs, normal oxygen saturation, progression with ventilator weaning if appropriate, return to normal level of orientation, and a quiet yet arousable state.

Adult↗