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Biomedical subjects

M Friedman

Publications and source records attributed to M Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1999

Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.

STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double-blind, randomized, prospective, parallel group studies comparing the long-term efficacy and safety of ipratropium combined with albuterol in a single inhalational canister against either bronchodilator agent alone in patients with COPD. PATIENTS: One thousand sixty-seven patients with COPD. METHODS: The dose of each bronchodilator was two puffs four times a day (42 microg of ipratropium bromide, 240 microg of albuterol sulfate). Pulmonary function testing was performed on days 1, 29, 57, and 85 of treatment. Outcomes, health-care resource consumption, and costs were compared for the three treatment groups over the 85-day study period. A total of 1,067 patients were randomized in the two studies (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus ipratropium, n = 358). RESULTS: Improvement in FEV1 and area under the FEV1 response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for the combination of albuterol plus ipratropium than either agent alone on all test days. Compared with albuterol, patients receiving ipratropium and ipratropium plus albuterol experienced significantly fewer COPD exacerbations and patient-days of exacerbation. In addition, the increased frequency of exacerbations observed in the albuterol group was associated with a significant increase in the number of patient hospital days and antibiotic and corticosteroid use. As a result, the total cost of treatment over the study period was significantly less for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per patient) than for albuterol ($269 per patient). Increased cost-effectiveness, defined as total estimated treatment cost per mean change in FEV1AUC0-4, was observed in both treatment arms containing ipratropium. CONCLUSIONS: The inclusion of ipratropium in a pharmacologic treatment regimen is associated with a lower rate of exacerbations in COPD. The result is lower total treatment costs and improved cost-effectiveness.

Adult↗
PubMed1999

Prevalence of malingering in suicidal psychiatric inpatients: a replication.

The MMPI-2, L, F, and K validity scales were administered to 21 (42%) suicide attempters and 29 (58%) ideators who had been hospitalized as being at risk for committing suicide. These inpatients were also asked to rate anonymously how much they had "exaggerated on purpose or lied about being suicidal to a staff member" during their current hospitalizations. The three MMPI-2 validity scores of the inpatients were not associated with self-reported malingering, and 6 (12%) of the inpatients reported malingering. This rate was comparable to the 10% rate which had previously been found by Rissmiller, et al. in 1998.

Adult↗
PubMed1999

The myocardial profile of the cytosolic isozymes of creatine kinase is apparently not related to cyanosis in congenital heart disease.

BACKGROUND: CKMB, the cardiac-specific heterodimer of cytosolic creatine-kinase (CK), is developmentally and physiologically regulated, tissue hypoxia being a proposed regulator. In patients with cyanotic heart disease the myocardium is perfused with partially saturated blood. We questioned whether the myocardium of cyanotic subjects contains higher proportions of CKMB. MATERIALS AND METHODS: CK activity, the distribution of cytosolic CK isozymes, activity of lactic dehydrogenase (LDH), and tissue protein content were determined in obstructive tissues removed at corrective surgery of patients with congenital heart defects. Cyanotic (n = 13) and acyanotic (n = 12) subjects were compared. RESULTS: In cyanotic and acyanotic patients, CK activity was 8.4 +/- 0.6 and 7.6 +/- 0.6 IU/mg protein and the proportion of CKMB was 21 +/- 1.4 and 22 +/- 2. 0% (mean +/- S.E.M), respectively. In the two groups of patients, the activity related to the B subunit corresponded to the steady-state level of the CKBmRNA. The tissue content of protein and the activities of CK and LDH were similar in cyanotic and acyanotic subjects and increased with the age. CONCLUSIONS: The lack of difference in CKMB distribution between the cyanotic and acyanotic patients may either indicate that hypooxygenation is not a regulator of CK isozyme expression, or may be attributed to the already high proportion of this isozyme in hypertrophied, obstructive tissues. Recruitment of additional CKMB, in the cyanotic hearts, may thus not be required.

Adolescent↗
PubMed1999

The economic cost of Alzheimer's disease and related dementias to the California Medicaid program ("Medi-Cal") in 1995.

Although state Medicaid programs may bear a large portion of the costs of Alzheimer's disease (AD), current information on spending is not available. Using a health insurance claims database for a 10% random sample of California Medicaid ("Medi-Cal") recipients 60+ years of age, the authors estimated the excess cost of AD to Medi-Cal in 1995 as the difference in expenditures between an AD cohort (those with AD or related dementias) and an age- and sex-matched cohort without AD. Among 62,450 recipients, 2,575 (4.1%) were found to have AD or related dementias, and their average payments were approximately $7,700 higher (P<0.01) than those for the comparison group. These estimates suggest that Medi-Cal spends about $200 million on AD and related dementias annually, a burden that represents nearly 10% of state spending on elderly patients.

Aged↗
PubMed1999

Dental drug-delivery devices: local and sustained-release applications.

Dental diseases are among the most prevalent illnesses in humans. Many pharmaceutical dosage forms are used to prevent and treat these diseases. Toothpastes and mouthwashes are two of the most popular dental medicaments. A local delivery application that prolongs the release of the drug in the mouth offers great advantages in preventing and treating caries and periodontal diseases. Sustained-release devices are a relatively new concept in dentistry. This paper describes several types of sustained-release devices that are available commercially or are in the premarketing stage.

Adhesives↗
PubMed1999

Microscope-assisted precision dentistry.

To enhance their vision for both clinical and laboratory procedures, an increasing number of dental practitioners are introducing magnification into their practices. Most are using either simple or compound loupes mounted on glasses frames. And although magnification is not new to dentistry, it is a trend that is gaining a broader acceptance among both seasoned practitioners and recent graduates. Many dental schools are allowing their students to use loupes on a discretionary basis, so the notion that magnification is reserved only to compensate for deteriorating vision is rapidly disappearing. Dental professionals have also begun to recognize that the quantity and quality of light in the working field is just as important as magnification. Headlamps with focused, color-correct light sources in combination with loupes are becoming popular. It is highly unlikely that a practitioner using loupes would relinquish them and return to practicing without magnification. The newest addition to the vision enhancement arena in dentistry is the operating microscope. In some medical subspecialties--such as otolaryngology, ophthalmology, plastic surgery, and neurosurgery--extensive microsurgical training is required to perform procedures at acceptable standards of precision. In 1998, the American Association of Endodontists (AAE) elected to mandate that all endodontic postgraduate students demonstrate proficiency using an operating microscope before they receive their certificates. Microscope use has also been reported in periodontics. For several decades, many dental laboratory technicians have used stereomicroscopes for trimming dies, refining castings, and performing other procedures that require a high degree of precision. However, according to microscope manufacturers, most current instrument sales are to general practitioners, who are not limiting the use of their microscopes to endodontic therapy--they are using them for a wide variety of procedures. Microscopes have the potential to enhance a dental practitioner's vision to unprecedented levels, but there are some practical questions that need to be addressed. What kind of visual acuity do dentists really need to perform high-quality dentistry? If a dentist wants to improve his or her vision, do loupes provide an adequate level of magnification? Is using a microscope too complicated for restorative and prosthodontic procedures, and how long does it take to become proficient with a microscope? These are some of the questions I posed to two outstanding dentists who have had extensive clinical experience using surgical microscopes. I also share my own experience with a microscope.

Dental Equipment↗
PubMed1998

Spatiotemporal tuning of low-frequency cells in the anteroventral cochlear nucleus.

Low-frequency cells in the anteroventral cochlear nucleus (AVCN) can be sensitive to changes in the spatiotemporal pattern of discharges across their auditory nerve (AN) inputs (). This sensitivity suggests that these cells may be tuned to particular spatiotemporal patterns, or features, in the discharge patterns of populations of AN fibers. To evaluate and characterize this sensitivity, we developed a technique whereby the physiological responses of AVCN cells to wide-band noise were analyzed using the simulated response of a population of AN fibers to the same noise stimulus. By averaging the simulated two-dimensional spatiotemporal pattern of AN activity that preceded each AVCN discharge, it was possible to derive a two-dimensional reverse-correlation function that characterized the spatiotemporal tuning of each AVCN cell. The derived spatiotemporal tuning pattern represented a feature in the AN population response that was most likely to precede discharges of the AVCN cell. To test the spatiotemporal tuning characterizations, we used these patterns to predict the responses of cells to noise stimuli statistically independent from the stimuli used to characterize the cells. This technique provides a general tool for the study of any neural system that involves the analysis of spatiotemporal input patterns.

Acoustic Stimulation↗
PubMed1998

Lipid ozonation products activate phospholipases A2, C, and D.

Ozone exposure, in vitro, has been shown to activate phospholipases A2 (PLA2), C (PLC), and D (PLD) in airway epithelial cells. However, because of its high reactivity, ozone cannot penetrate far into the air/lung tissue interface. It has been proposed that ozone reacts with unsaturated fatty acids (UFA) in the epithelial lining fluid (ELF) and cell membranes to generate a cascade of lipid ozonation products (LOP) that mediate ozone-induced toxicity. To test this hypothesis, we exposed cultured human bronchial epithelial cells (BEAS-2B) to LOP (1-100 microM) produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and measured the activity of PLA2, PLC, and PLD. The PLA2 isoform responsible for arachidonic acid release (AA) in stimulated cultures was also characterized. Activation of PLA2, PLC, and PLD by three oxidants, hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) also was measured and compared to that of LOP. The derivatives of ozonized POPC at the sn-2 residue, 9-oxononanoyl (PC-ALD), 9-hydroxy-9-hydroperoxynonanoyl (PC-HHP), and 8-(-5-octyl-1,2,4-trioxolan-3-yl-) octanoyl (POPC-OZ) selectively activated PLA2 in a dose-dependent fashion. Cytosolic PLA2 (cPLA2) measured in the cytosolic fraction of stimulated cell lysates was found to be the predominant isoform responsible for AA release. PLC activation was exclusively induced by the hydroxyhydroperoxide derivatives. PC-HHP and the 9-carbon hydroxyhydroperoxide (HHP-C9) increased PLC activity. PLD activity also was induced by LOP generated from POPC. Incubation of cultures with H2O2 alone did not stimulate PLC; however, in the presence of the aldehyde, nonanal, a 62 +/- 2% increase in PLC activity was found, suggesting that the increase in activity was due to the formation of the intermediate HHP-C9. t-BOOH, and AAPH also failed to induce PLA2 activation, but did activate PLC, under conditions of exposure identical to that of LOP. Only t-BOOH activated PLD. These results suggest that biologically relevant concentrations of LOP activate PLA2, PLC, and PLD in the airway epithelial cell, a primary target to ozone exposure. The activation of these phospholipases may play a role in the development of lung inflammation during ozone exposure.

Arachidonic Acid↗
PubMed1998

Pharmacodynamic and pharmacokinetic rationales for the development of an oral controlled-release amoxicillin dosage form.

The goal of this investigation was to develop an oral sustained-release formulation for amoxicillin that would maximize the duration of active drug concentration in the extracellular fluid, thus increasing the dosing interval while assuring antimicrobial activity. This rationale is based on the pharmacodynamic properties of the drug which is non- concentration dependent on the one hand, while requiring long exposure of the pathogen to the drug with minimal post-antibiotic effect on the other. Due to pharmacokinetic constraints, including short biological half-life and limited 'absorption window' (confined to the small intestine) with poor colonic absorption, the new matrix tablet formulation, composed of hydrophilic (hydroxypropyl methyl-cellulose) polymer, was designed to release 50% of its contents within the first 3 h and to complete the drug release process over 8 h (under in vitro conditions). The pharmacokinetics of the new formulation was evaluated in 12 healthy volunteers and compared to a conventional gelatin capsule with both formulations containing 500 mg amoxicillin. The plasma concentrations of active amoxicillin and penicilloic acid were determined by an HPLC method with a fluorometric detector. It was found that the area under the concentration-time curve and maximal serum amoxicillin concentrations following the sustained release preparation were lower than the immediate release formulation. However, the time over the required threshold concentrations, i.e. the minimal inhibitory concentration (MIC) as well as the more clinically relevant parameter--four times MIC of the drug against susceptible pathogens, was found to be maintained for significantly longer periods. The results suggest that in order to achieve a twice daily dosing regimen that will provide therapeutic concentrations for the whole 12 h dosing intervals, a larger dose of the new formulation should be given (e.g. 750 mg or even 1 g twice daily). This recommendation is based on the large interindividual differences of the extent of amoxicillin absorption found in this investigation, and is intended to assure that the 'poor' absorbers will also benefit from full antibiotic efficacy. This dosing regimen will lead to increased patient compliance and improved therapeutic outcome.

Administration, Oral↗
PubMed1998

Crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets based on hydroxypropyl methylcellulose.

The influence of hydroxypropyl methylcellulose (HPMC) on the crystal habit properties of carbamazepine in sustained release matrix tablets and in aqueous solutions was investigated using differential scanning calorimetry (DSC), X-ray powder diffraction and scanning electron microscopy (SEM). The results suggest that HPMC inhibits the transformation of carbamazepine to carbamazepine dihydrate in the gel layer of hydrated tablets and in aqueous solutions (depending on HPMC concentration), participates in its crystallization process and induces amorphism of carbamazepine crystals. The mechanism which explains these effects envisages the polymer serving as a template or microsubstrate for nucleation in the crystallization process. We assume that the interaction between the drug and polymer occurs by hydrogen bonding. The hydroxyl groups of the polymer may attach to the drug at the site of water binding, and thus its transformation to the dihydrate form, is inhibited. A more specific interaction involves structural matching (similar bond spacing distances) between inter-atomic distances in the crystal lattice of carbamazepine dimer and intra-atomic distances along the polymer chain.

Calorimetry, Differential Scanning↗
PubMed1998

Developmental toxicology of solamargine and solasonine glycoalkaloids in frog embryos.

As part of an effort to improve the safety of plant foods, a need exists to define the relative toxicities of structurally different glycoalkaloids and metabolites which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. The objectives of this study were to determine the relative toxicities and the modes of action of the eggplant (Solanum melongena) glycoalkaloids solamargine and solasonine in Xenopus laevis frog embryos, using membrane potential and embryo growth and teratogenicity assays. In the cell membrane assays, adverse effects on embryos were evaluated by measuring membrane potentials using an electrochromic dye, di-4-ANEPPS, as a fluorescence probe for the integrity of the membranes. In the embryo growth and teratogenesis assays, the survival of the embryos and organ malformations was used as an index of embryo toxicity. The relative potencies of glycoalkaloids are similar for frog embryo effects (survival and teratogenicities) and for membrane effects (membrane potential). Experiments with solasonine at pH 6 and 8 suggest that the unprotonated form of the glycoalkaloids appears to be involved in the membrane effects. The nature of the carbohydrate side-chains of the steroidal glycosides governs relative potencies. The possible significance of the findings to food safety and plant physiology and possible application of the membrane assays to bacterial toxins are discussed.

Animals↗
PubMed1998

In vitro assessment of the antimicrobial activity of a local sustained release device containing amine fluoride for the treatment of oral infectious diseases.

Dental caries and periodontal diseases are chronic infectious diseases caused by oral bacteria. Local sustained release delivery systems extend the time in which the drug is present in the oral cavity, thus enhancing its therapeutic potential while reducing its side effects. Amine-fluorides (AmF) are known anticaries agents and have recently been found to have an antibacterial effect against periodontal pathogens and caries-associated bacteria. The purpose of this in vitro study was to assess the antimicrobial activity of a local sustained release device (LSRD) containing AmF on Streptococcus sobrinus 6715. LSRD was prepared from an ethylcellulose matrix containing AmF. Release kinetics of AmF from the LSRD was measured simultaneously with its antimicrobial activity. The organic amine and the fluoride were released in different kinetics profiles: The fluoride was released faster than the organic amine. The antimicrobial activity of AmF was measured on planktonic bacteria in solution and on bacteria as part of experimental dental plaque. During a 10-day period, the concentration of the released AmF was above its MIC and no bacterial growth was observed. Bacterial counts in the dental plaque were reduced by 1 to 2 log units. Hence, the LSRD containing AmF has the potential to serve as a medicament in prevention and treatment of dental caries and periodontal diseases.

Anti-Infective Agents, Local↗
PubMed1998

The time course of visuospatial processing deficits in schizophrenia: an event-related brain potential study.

Event-related brain potentials (ERPs) were recorded during a dot enumeration task so as to investigate electrophysiologic correlates of early visuospatial processing in schizophrenia. Twenty-eight patients having a diagnosis of schizophrenia (n = 19) or schizoaffective disorder (n = 9) and 28 controls were tested. Patients showed poorer dot enumeration than did controls and also had markedly reduced early negative ERPs, which began about 150 ms after stimulus onset at the peak of the N1 potential and reached its maximum about 275 ms at the N2 peak. The N1 reduction in patients was greatest over left parietal sites for stimuli in the right visual field. The marked N1 and N2 reductions in patients are supportive of models postulating deficits in early visuospatial attention and allocation of conceptual resources in schizophrenia.

Adult↗
PubMed1998

Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha.

Peroxisome proliferator activated receptors (PPAR) belong to the superfamily of nuclear hormone receptors that heterodimerize with the retinoid X receptor and regulate transcription of several genes involved in lipid metabolism and adipocyte differentiation. Because of the role of 1,25-dihydroxyvitamin D3 and retinoic acid working through similar receptors (the vitamin D receptor and retinoic acid receptor, respectively) on keratinocyte differentiation, we have examined the effects of activators of PPARalpha on keratinocyte differentiation. The rate of cornified envelope formation was increased 3-fold in keratinocytes maintained in low calcium (0.03 mM) and incubated in the presence of clofibric acid, a potent PPARalpha activator. Involucrin, a cornified envelope precursor, and the cross-linking enzyme transglutaminase, were increased at both the message level (2-7-fold) and the protein level (4-12-fold) by clofibric acid. Furthermore, physiologic doses of the fatty acids oleic acid, linoleic acid, and eicosatetraynoic acid, which are also activators of PPARalpha, also induced involucrin and transglutaminase protein and mRNA. In contrast, the PPARgammaligand prostaglandin J2 had no effect on protein or mRNA levels of involucrin or transglutaminase. Levels of involucrin and transglutaminase mRNA and protein were induced by clofibric acid in keratinocytes incubated in 1.2 mM calcium, a concentration which by itself induces keratinocyte differentiation. Finally, PPARalpha activators inhibit DNA synthesis. This study demonstrates that PPARalpha activators, including putative endogenous ligands such as fatty acids, induce differentiation and inhibit proliferation in keratinocytes, and suggests a regulatory role for the PPARalpha in epidermal homeostasis.

Cell Differentiation↗
PubMed1998

Regulators of proliferation and apoptosis in carcinoma of the larynx.

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.

Adult↗
PubMed1998

The effect of the mode of administration on the hypolipidaemic activity of niacin: continuous gastrointestinal administration of low-dose niacin improves lipid-lowering efficacy in experimentally-induced hyperlipidaemic rats.

The effect of different routes and modes of administration of niacin (nicotinic acid) on its hypolipidaemic activity has been evaluated. Our working hypothesis was that the major sites of niacin action are located presystemically (i.e. in the gut wall or the liver, or both) which would make niacin a gastrointestinal drug. For such drugs continuous administration to the gastrointestinal tract is expected to augment their efficacy compared with bolus oral administration or parenteral administration. The hypothesis was examined in two rat models of experimentally induced hyperlipidaemia-Model A, based on a cholesterol-enriched diet, and Model B, in which acute hyperlipidaemia is induced by intraperitoneal administration of triton (225 mg kg(-1)). Continuous administration of niacin into the duodenum at 1.66 mg h(-1) (total dose 40 mg kg(-1) day(-1)) for up to 7 days (Model A) or at 2.22 mg h(-1) over 18 h (Model B) had significantly greater lipid-reducing effects both on total cholesterol and on triglyceride levels (15-25%) and elevation of high-density lipoprotein (HDL) cholesterol levels than did bolus oral administration of the same dose. Continuous duodenal infusion of niacin also had an even greater lipid-reducing effect than continuous intravenous infusion of the drug at the same rate and dose. The results indicate that the site(s) of action are located presystemically and that continuous duodenal administration of a low dose of niacin (40 mg kg(-1)) has a greater lipid-lowering effect than a higher dose (200 mg kg(-1)) administered by peroral bolus administration. These conclusions were validated by administration of a specially designed niacin sustained-release matrix tablet formulation that was non-invasively administered to hyperlipidaemic rats. The hypolipidaemic activity of the sustained-release tablet was of similar magnitude to that resulting from continuous duodenal administration, thus providing a pharmacodynamic rationale for this mode of administration.

Animals↗