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Biomedical subjects

L Diamond

Publications and source records attributed to L Diamond.

At least 19 recordsLinked to original sources
PubMed2000

Managing obesity like any other chronic condition. Long-term therapy may reduce comorbidity as well.

Patients often seek help from their primary care physician for weight loss, so familiarity with pharmacologic options and their risks is important. Anorexiants have been available for decades and are relatively safe. Orlistat and sibutramine are two of the newer medications that patients may have heard about in television, newspaper, and magazine advertising. In addition, patients often ask for advice regarding various herbal or nonprescription medications for weight loss. In this article, the authors help physicians prepare to address these questions.

Anti-Obesity Agents↗
PubMed1997

CD46 expression does not overcome the intracellular block of measles virus replication in transgenic rats.

The study of measles pathogenesis and the testing of improved vaccine candidates is hampered by the lack of a small animal model which is susceptible to infection by the intranasal route. With the identification of CD46 as a measles virus (MV) receptor, it was feasible to generate transgenic rats to overcome this problem. Although there was widespread expression of CD46 in the transgenic Sprague-Dawley rats, no measles-like disease could be induced after various routes of infection. The expressed transgenic protein was functionally intact since it mediated MV fusion and was downregulated by contact with MV hemagglutinin. In vitro studies revealed that CD46-expressing rat fibroblasts take up MV but do not allow viral replication, which explains the nonpermissiveness of the transgenic rats for in vivo infection.

Animals↗
PubMed1996

Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds. DESIGN: Multicenter, double-blind, randomized trial. SETTING: 3 university student health services. PATIENTS: 411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period. INTERVENTION: Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods. RESULTS: Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5). CONCLUSIONS: Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds.

Administration, Intranasal↗
PubMed1996

RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.

An activated ras oncogene induces a program of differentiation in the human medullary thyroid cancer cell line TT. This differentiation process is accompanied by a marked increase in the transcription of the human calcitonin (CT) gene. We have localized a unique Ras-responsive transcriptional element (RRE) in the CT gene promoter. DNase I protection indicates two domains of protein-DNA interaction, and each domain separately can confer Ras-mediated transcriptional inducibility. This bipartite RRE was also found to be Raf responsive. By affinity screening, we have cloned a cDNA coding for a zinc finger transcription factor (RREB-1) that binds to the distal RRE. The consensus binding site for this factor is CCCCAAACCACCCC. RREB-1 is expressed ubiquitously in human tissues outside the adult brain. Overexpression of RREB-1 protein in TT cells confers the ability to mediate increased transactivation of the CT gene promoter-reporter construct during Ras- or Raf-induced differentiation. These data suggest that RREB-1 may play a role in Ras and Raf signal transduction in medullary thyroid cancer and other cells.

Adult↗
PubMed1996

Methylphenidate augmentation of serotonin selective reuptake inhibitors: a case series.

BACKGROUND: The serotonin selective reuptake inhibitors (SSRIs) are effective in treating major depressive episodes. However, for the subgroups of patients who remain refractory to therapy, augmentation strategies can improve the efficacy of these agents. METHOD: We report the results of an open trial of methylphenidate to augment SSRIs in the treatment of five consecutive cases of DSM-III- R diagnosed major depression. RESULTS: Self-reported symptom reduction was achieved rapidly in all cases, with methylphenidate dosages ranging from 10 to 40 mg/day. Symptom remission was independent of the presence of attention-deficit/hyperactivity disorder. Also, the beneficial effects of the methylphenidate-SSRI combination appeared to be robust and sustained. No patients abused or misused methylphenidate. CONCLUSION: The empirical use of methylphenidate added to ineffective or only partially effective SSRI treatment appeared to be a rapid, safe, and efficacious alternative to existing augmentation strategies for the treatment of major depression. Prospective controlled studies are required to confirm or refute these findings.

Adult↗
PubMed1995

A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.

Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.

Adolescent↗
PubMed1994

Measuring, managing, and improving quality in the end-stage renal disease treatment setting: committee statement.

The Institute of Medicine (IOM) committee that organized the conference reported in this issue of the journal on assessing quality of care and quality of life, wishes to emphasize that it regards the task of measuring quality as one that can be approached systematically, albeit with caution. Outcomes of end-stage renal disease (ESRD) care by dialysis and transplantation (and variations of outcomes among treatment units) and related processes of care need to be measured in ways useful to clinicians. In addition to clinical measures of outcome, the committee also favored giving greater attention to functional outcomes and health-related quality of life. The interest in maintaining and improving quality in the treatment setting reflects an underlying need to encourage its systematic assessment on a sustained basis, with appropriate weight devoted to practical issues.

Humans↗
PubMed1994

Sensory evaluation of oral nutritional supplements: a comparison of patient and dietitian preferences.

The choice of oral nutritional supplements (ONS) is typically made by a formulary committee without patient input. The purpose of this study was to determine if significant differences arose in the following two areas: (1) in preference of ONS between patients and dietitians/dietetic interns; and (2) between ONS from different companies as detected by either patients or dietitian/dietetic interns. ONS in the 1.0 kcal/mL and 1.5 kcal/mL lactose-free category from five companies, in all flavors, were randomly evaluated by 392 patients and 34 dietitians/dietetic interns. Each product was evaluated using a seven-point hedonic scale. When more than one brand of the same flavor was present, products were than ranked in order of preference. There were significant differences between patients and dietitians/dietetic interns in their evaluation of 7 of the 13 product lines. Significant differences were also found between same-flavored products of equal caloric density produced by different companies. Since the patients typically rated the ONS as more acceptable when a difference did exist, it would appear unnecessary for formulary committees to test products on the patient population on a regular basis.

Alberta↗
PubMed1994

Transformation of diploid human lung fibroblasts with oncogene ras increases the frequency of abnormal mitoses.

The human oncogene ras p21 was transfected into human lung fibroblast WI-38 diploid cells. All of the clones that were isolated (n = 36), exhibited rapid growth and transformed morphology which was ascertained by both transmission and scanning electron microscopy as extensive formations of microvilli on the plasma membrane, marked distortion of the nuclear membrane and increased number of pinocytotic vesicles in the cortical cytoplasm. The frequency of abnormal metaphases rose from 15% in parental WI-38 cells to 35.5-48.4% in all ten clones examined. Lagging chromosomes in prometaphase represented 42.1-69.4% of the total abnormal mitoses followed in frequency by 3-group metaphase and C-metaphase. All transformed cells were aneuploid. These data provide evidence for the association between cellular transformation with oncogenic ras and elevated abnormal mitoses in human cells.

Aneuploidy↗
PubMed1992

Atypical presynaptic alpha-adrenoceptor modulation of neurally-mediated cholinergic responses in guinea-pig tracheal smooth muscle.

Cholinergic excitatory nerves in guinea-pig trachea are subject to inhibitory control by presynaptic alpha 2-adrenoceptors. Recently, the nature of these receptors has come into question insofar as the presynaptic inhibitory effects of the alpha 2-adrenoceptor agonist, clonidine, in the guinea-pig trachea have been shown to be antagonized by the alpha 2-adrenoceptor antagonist, yohimbine, as well as the alpha 1-adrenoceptor antagonist, prazosin. This inhibitory action of prazosin had not been described previously in the airways and may relate to the use of norepinephrine rather than clonidine as the alpha-adrenoceptor agonist in earlier studies. The present study evaluates the susceptibility of norepinephrine-induced inhibition of neurally-mediated cholinergic excitatory responses to antagonism by prazosin and yohimbine under conditions identical to those which showed clonidine to be sensitive to these antagonists. In tissues pretreated with guanethidine, propranolol and indomethacin, norepinephrine (1 microM) induced a 37-fold rightward shift of the frequency-response curve for neurally-mediated cholinergic contractions which was reversed partially by pretreatment of tissues with yohimbine. Norepinephrine also caused a concentration-dependent inhibition of cholinergic 'twitch' responses induced by intermittent (1 Hz) nerve stimulation. This action of norepinephrine was antagonized in a concentration-dependent manner by yohimbine but was unaffected by prazosin. These results indicate that in guinea-pig trachea the presynaptic inhibitory actions of norepinephrine on cholinergic nerves are mediated via classical alpha 2-adrenoceptors, i.e. receptors that can be blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cigarette smoke exposure does not prevent cadmium-induced alterations in rat lungs.

Cigarette smoke has been demonstrated to suppress the biosynthesis of connective tissue in the lung. To further characterize this suppressant effect, we studied the ability of cigarette smoke to prevent or ameliorate cadmium-induced alterations in rat lungs in vivo. The effects of beta-aminopropionitrile (beta APN), an agent that inhibits the cross-linking of elastin, also were studied. Eighty-eight young female Long-Evans rats were randomly divided into seven groups as follows: control, cigarette smoke, sham smoke, beta APN, cadmium, cadmium + cigarette smoke, and cadmium + beta APN. Each animal in the cigarette smoke group was exposed to mainstream smoke generated from University of Kentucky 2R1 reference cigarettes (10 puffs daily for 12 wk). Sham-treated animals received room air in place of cigarette smoke. beta APN (0.5 g/kg) was injected intraperitoneally twice weekly. In cadmium-treated groups, each rat received intermittently three intratracheal instillations of cadmium chloride (0.15 mumol/kg) over a 5-d period. For the cadmium + cigarette smoke group, smoke exposure began 3 d after the first cadmium instillation and was continued for 12 wk. The beta APN administration began 5 d before cadmium instillation and also was continued for 12 wk. After these treatments, pulmonary function and lung morphometry were examined. Neither cigarette smoke, sham smoke, nor beta APN produced significant changes in lung function or morphometry. Cadmium caused significant decreases in total lung capacity, dynamic and static compliance, and carbon monoxide diffusing capacity, as well as significant increases in lung weight and alveolar wall thickness. In addition, the quasistatic deflation pressure-volume curve showed a rightward shift whereas the mean linear intercept of the alveoli did not change significantly. Efforts to prevent or ameliorate the changes through exposure to cigarette smoke or administration of beta APN were unsuccessful. It is concluded that interventions designed to inhibit the biosynthesis of lung connective tissue do not perforce inhibit the development of cadmium-induced pulmonary changes in the rat.

Animals↗
PubMed1992

Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways.

omega-Conotoxin GVIA, a peptide derived from the marine snail Conus geographus, is an antagonist of the neuronal N type voltage-sensitive calcium channels associated with neurotransmitter release. The present study investigated effects of this peptide on neurally mediated responses in airways isolated from the guinea pig to determine whether airway nerves are modulated by omega-conotoxin-sensitive calcium channels. Electrical field stimulation was used to induce neurally mediated tachykininergic excitatory responses in guinea pig bronchus and cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. Exogenous agonists were administered to induce contractile (acetylcholine, substance P) or relaxation (sodium nitroprusside) responses. Tissues were incubated with omega-conotoxin (1 microM) or its vehicle (10 mM acetic acid) for 30 min before establishing frequency- or concentration-response relationships to the various stimuli. Frequency-response curves for neurally mediated cholinergic, nonadrenergic nocholinergic inhibitory and tachykininergic responses were shifted to the right by omega-conotoxin to a similar extent (4- to 5-fold). omega-Conotoxin had no effect on contractile responses elicited by exogenous acetylcholine or substance P or on relaxations induced by sodium nitroprusside. These findings indicate that neurotransmission in afferent tachykininergic kininergic nerves and in efferent cholinergic excitatory and nonadrenergic noncholinergic inhibitory nerves in the airways is modulated by a prejunctional omega-conotoxin-sensitive mechanism.

Acetylcholine↗