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S Diamond

Publications and source records attributed to S Diamond.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1.

A research program targeted toward the identification of expanded-spectrum nonnucleoside reverse transcriptase inhibitors which possess increased potency toward K103N-containing mutant human immunodeficiency virus (HIV) and which maintain pharmacokinetics consistent with once-a-day dosing has resulted in the identification of the 4-cyclopropylalkynyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 961 and DPC 963 and the 4-cyclopropylalkenyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 082 and DPC 083 for clinical development. DPC 961, DPC 963, DPC 082, and DPC 083 all exhibit low-nanomolar potency toward wild-type virus, K103N and L100I single-mutation variants, and many multiply amino acid-substituted HIV type 1 mutants. This high degree of potency is combined with a high degree of oral bioavailability, as demonstrated in rhesus monkeys and chimpanzees, and with plasma serum protein binding that can result in significant free levels of drug.

Amino Acid Substitution↗
PubMed1998

A novel angiotensin II binding site in murine tissues.

A novel binding site for angiotensin II has been identified in certain murine tissues. This site, denoted ATm, is distinct from both the AT1 and AT2 sites, as well as the various atypical sites that have been described. The site has a low affinity for angiotensin II (100 nM) and is not blocked by losartan, PD123177 or saralasin. The site shows structural specificity for angiotensin II since both angiotensin III and angiotensin II (1-7) failed to inhibit the binding. Numerous standard drugs, including various receptor blockers, enzyme inhibitors and therapeutic agents, showed no affinity for the site. In murine tissues the site is associated with active tissue generation, as found in spleen, placenta and growing tumors, but its occurrence appears to be rare outside of the mouse.

Amino Acid Sequence↗
PubMed1998

Flow cytometric analysis of lymphocyte subsets in migraine patients during and outside of an acute headache attack.

We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases (n = 5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers (n = 12; group E). Comparison of the first set of lymphocytes (CD3+CD16 + 56+, CD3-CD16 + 56+, CD3-CD19+, CD3+CD19+, and CD3+HLA - DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3+CD16 + CD56+ and CD3-CD19+ lymphocytes. Furthermore, these differences reached statistical significance only for the CD3+CD16 + CD56+ lymphocytes, and then solely for the patients in group C (Scheffe's test, p < 0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3+CD16 + CD56+ lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3+CD16 + CD56+ lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition.

Acute Disease↗
PubMed1998

Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports.

With the use of the newer antidepressants beyond the traditional tricyclics and monoamine oxidase inhibitors, newer options in headache prophylaxis are provided as well as the potential for undesirable and even potentially life-threatening interactions between medications. In this article, four patient reports of a specific interaction--the serotonin syndrome--are presented. These events resulted from transitioning headache patients from an older antidepressant (phenelzine) to a newer antidepressant (venlafaxine).

Adult↗
PubMed1997

A randomized controlled trial of penicillin vs clindamycin for the treatment of aspiration pneumonia in children.

OBJECTIVE: To compare the effectiveness of intravenous penicillin vs clindamycin for the treatment of aspiration pneumonia. DESIGN: A double-blind, randomized controlled trial. SETTING: A tertiary care pediatric hospital. PATIENTS: We enrolled 42 children, aged 6 months to 18 years, who were admitted to the hospital for the treatment of aspiration pneumonia. All of the children had underlying conditions that predispose to aspiration. INTERVENTION: The patients were randomly assigned to receive intravenous penicillin G sodium, 250,000 U/kg every 24 hours, or intravenous clindamycin phosphate, 30 mg/kg every 24 hours. MAIN OUTCOME MEASURE: The primary outcome measure was "time to ready for discharge" from the hospital. RESULTS: In an effectiveness (intention to treat) analysis, the median time (interquartile range) to ready for discharge from the hospital was 4.9 days (range, 2.8-6.5 days) in the penicillin-treated group and 3.4 days (range, 2.3-6.8 days) in the clindamycin-treated group (P = .66). Results were not markedly altered when adjusted for the age difference of the groups or in the efficacy analysis (after the exclusion of 9 patients who withdrew from the trial). Rates for readmission to the hospital were similar in the 2 groups. CONCLUSION: Penicillin and clindamycin seem to be equally effective for the treatment of aspiration pneumonia in children hospitalized for this illness.

Adolescent↗
PubMed1997

Spontaneous duodenal hematoma in a patient with Glanzmann's thrombasthenia.

Spontaneous intramural duodenal hematoma is a rare problem, most commonly seen in children who have coagulation disorders. A child who had Glanzmann's thrombasthenia, a disorder of platelet function, presented with signs and symptoms of duodenal obstruction. Nonoperative management of an obstructing duodenal hematoma was successful and potentially life-threatening surgery was avoided.

Abdominal Pain↗
PubMed1997

Emergency treatment of migraine. Insights into current options.

The physician confronted with a headache patient in acute distress must establish the diagnosis before initiating therapy. Although the typical treatment in the emergency department has been to rely on narcotic analgesics, many safer alternatives are available. With all these therapeutic options to choose from, fewer patients should run the risk of narcotic addiction because of migraine attacks. To prevent a patient from becoming a frequent emergency department visitor, referral for prophylactic treatment is essential.

Acute Disease↗
PubMed1997

In vitro and in vivo effects of the arylamine human immunodeficiency virus protease inhibitor 4R-(4alpha,5alpha,6beta, 7beta)-1-[(3-(1-imidazoylcarbamoyl)phenyl)methyl]-3-[(3-aminophenyl)m ethyl]hexahydro-5,6-dihydroxy-4,7-bis(phenylmethyl)-2H-1, 3-diazepin-2-one (SD894) on rat hepatic cytochrome P450 2B and 3A.

The human immunodeficiency virus-1 protease inhibitor SD894 was evaluated as an inhibitor and inducer of cytochromes P450 (CYPs) in rats. After addition of 10 microM SD894 and 2 mM NADPH to liver microsomes from dexamethasone-treated rats, a type II spectrum appeared. Within 2 min, it was replaced by a type III spectrum, with absorbance maxima at 426 and 456 nm, similar to those observed with alkylamines (SKF-525A) and arylamines (p-chloroaniline). Preincubation of microsomes from dexamethasone-treated rats with SD894 and NADPH resulted in a time-dependent inhibition of testosterone 6beta-hydroxylation (CYP 3A1/2 activity), which was decreased to 25% of controls after 30 min. Testosterone 16beta-hydroxylation (CYP 2B1/2 activity) was unaffected under these conditions. Testosterone 6beta-hydroxylation rates in liver microsomes from pregnenolone 16alpha-carbonitrile-treated rats incubated with 10 microM SD894 and NADPH, washed, and reisolated by ultracentrifugation were reduced by 71%, whereas 16beta-hydroxylation was unaffected by SD894. Immunoblots of liver microsomes from rats dosed iv with SD894 or ip with TAO displayed increased CYP 2B1 and CYP 3A1 levels, respectively. Testosterone 6beta-hydroxylase activity in microsomes from TAO-treated rats was greater than controls. Preincubation of these microsomes with potassium ferricyanide produced an additional 50% increase, consistent with disruption of a metabolite-CYP complex. Microsomes from SD894-treated rats displayed a 3-fold increase in testosterone 16beta-hydroxylation. Potassium ferricyanide preincubation did not increase activity. Thus, although SD894 appears to inhibit CYP in vitro in a manner typical of other amine-containing, mechanism-based inhibitors, in vivo induction by 10 mg/kg daily doses of SD894 affects a different isozyme than does inhibition. The mechanism of induction is unknown.

Animals↗
PubMed1995

Transnasal butorphanol in the treatment of acute migraine.

We studied transnasal butorphanol (Stadol NS) for pain relief during acute migraine in a multicenter, randomized, double-blind, placebo controlled trial using ambulatory patients at 10 geographically diverse headache centers. Patients were volunteer adults diagnosed with migraine with or without aura by International Headache Society criteria. One hundred fifty-seven patients completed the study. We treated the pain of one headache in each patient with either transnasal butorphanol (n = 107) or transnasal placebo (n = 50). Pain relief, pain intensity, nausea, vomiting, and effect on function were measured periodically. Adverse experiences were documented. Global assessments were made at follow-up. With butorphanol, migraine pain was reduced from moderate, severe, or incapacitating to slight or absent for 35 patients (33%) within 30 minutes, for 50 patients (47%) within 1 hour, and for 76 (71%) within 6 hours, compared to 2 (4%), 8 (16%) and 15 (30%) respectively for placebo. Side effects were prominent, though confounded by the migraine. The most common side effects, compared to placebo, were dizziness (58% vs 4%), nausea and/or vomiting (38% vs 18%), and drowsiness (29% vs 0%). We conclude that transnasal butorphanol is a useful analgesic for the pain of acute migraine. Its prominent side effects and low self reinforcement rate may limit its usefulness in some patients, while increasing its appropriateness for others.

Acute Disease↗
PubMed1995

Excimer laser photorefractive keratectomy (PRK) for myopia--present status: aerospace considerations.

UNLABELLED: Excimer laser photorefractive keratectomy (PRK) to reduce myopia has been studied the past 3 yrs at multicenters authorized by the FDA. The excimer laser ablates the central cornea to a new calculated power. A review of the cases reported in the literature reveals the following information: Corneal scarring may be reflected in the loss of best-corrected vision. Regression of the refractive effect is a complication. Predictability was the percentage of eyes obtaining 20/40 or better vision; this varied from 62.5-91%. Conversely, 9.0-37.5% were 20/50 or worse. Low to moderate myopes had better visual success. Accuracy was the refractive correction within +/- 1.00 D (spherical equivalent); this varied between 64.7-93%. The higher percentages were with low to moderate degrees of myopia. Loss of best corrected vision was due to scarring and haze, and occurred more frequently with high myopia and deeper ablations. Patient satisfaction after 2 yrs was reported as 82.6-90%; 17.4% were not satisfied. ADVANTAGES: a) PRK effectively and safely corrected myopia and myopic astigmatism; b) there was no diurnal variation of refraction or vision; c) vision remained fairly stable with some regression up to 24 mo and; d) accuracy of correction to +/- 1.00 D was fair. Disadvantages: a) post-operative scarring and haze was present after 6 mo to 2 yrs of follow-up in some cases. Scarring was less with low myopia and worse with high myopia; b) regression of correction and blur; and c) poor night vision, halos, and glare sensitivity occurred after pupil dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗
PubMed1994

Hereditary variations in monoamine oxidase as a risk factor for Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies suggest that several genes may have a role in determining individual susceptibility to this disease, and the degradative enzyme monoamine oxidase (MAO) has been implicated in the disease process. Wide differences in activity levels for both forms of this enzyme (MAO-A and MAO-B) exist in the human population, and levels of both are genetically determined. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci on the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length polymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n repeat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was significantly different (p = 0.03) between these two groups. Another MAOA haplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0.046). These findings support the idea that the MAO genes may be among the hereditary factors that influence susceptibility of individuals to PD.

Adolescent↗
PubMed1993

Heparin and dibutyryl cAMP modulate gene expression in stimulated human saphenous vein smooth muscle cells.

Increased expression of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A chain, and tissue plasminogen activator (tPA) by smooth muscle cells (SMC) has been postulated to mediate the progression of intimal hyperplasia. We tested whether heparin would suppress the expression of these genes in stimulated human saphenous vein SMC. Quiescent cultured human saphenous vein SMC were stimulated for 4 h with heat-inactivated fetal bovine serum (10% by vol) in the presence or absence of heparin (1 to 250 micrograms/ml). Heparin (50 micrograms/ml) attenuated the induction by serum of bFGF mRNA, tPA mRNA, and tPA secretion. Nonanticoagulant heparin also attenuated serum induction of bFGF and tPA mRNA levels. To further study the role of second messenger signaling, a more specific mode of SMC stimulation was used with thrombin (3 U/ml) in the presence or absence of dibutyryl cyclic AMP (Bu2-cAMP; 0.5 mM). In contrast to heparin, which had no effect on PDGF expression, Bu2-cAMP decreased the induction by thrombin of PDGF-A chain mRNA levels. In thrombin-stimulated SMC, Bu2-cAMP significantly decreased secretion of PDGF-AA protein. Thrombin, however, caused an increase in bFGF mRNA levels which was potentiated by Bu2-cAMP with associated potentiation by Bu2-cAMP of intracellular bFGF protein levels. The induction of tPA mRNA and tPA secretion by thrombin was sharply blocked by Bu2-cAMP. These results suggest that heparin reduces intimal hyperplasia at least partly via partial inhibition of SMC gene expression.

Bucladesine↗