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Biomedical subjects

D J Friedman

Publications and source records attributed to D J Friedman.

At least 19 recordsLinked to original sources
PubMed2004

Fluocinolone acetonide topical oil for scalp psoriasis.

Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.

Administration, Topical↗
PubMed2000

Race/ethnicity and OMB Directive 15: implications for state public health practice.

OBJECTIVES: This study assessed the impact of the Office of Management and Budget's (OMB's) 1997 revised standards for the collection of race and ethnicity data on state health departments, using the Massachusetts Department of Public Health (MDPH) as the primary example, and we make recommendations for states' implementation of these standards. METHODS: After analyzing the revised OMB standards, existing MDPH data sets were assessed for the impact of the revised standards on data collection, tabulation, analysis, and reporting for state health departments. RESULTS: The revised OMB standards will have an impact on the MDPH and other state health departments. Similarities and differences exist between federal and state health agencies regarding the purpose of data collection, tabulation, analysis, and reporting. These similarities and differences will affect state implementation of the revised OMB standards. CONCLUSIONS: States need to plan for the implementation of the revised OMB standards and to understand the impact of this revision on the collecting and reporting of public health data. The revised OMB standards will introduce added complexities to the collection and analysis of race and ethnicity data, but they will also produce a more nuanced understanding of the relationship of race and ethnicity to the health of the American people.

Data Collection↗
PubMed1997

Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia.

BACKGROUND: Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS: The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q23 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS: Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purged autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS: These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

Acute Disease↗
PubMed1997

Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.

BACKGROUND: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Administration, Topical↗
PubMed1995

Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1.

Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies.

Base Sequence↗
PubMed1995

Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein.

Infection by human immunodeficiency virus-type 1 (HIV-1) is typified by the progressive depletion of CD4 T lymphocytes and deterioration of immune function in most patients. A central unresolved issue in acquired immunodeficiency syndrome (AIDS) pathogenesis is the mechanism underlying this T cell depletion. HIV-1 Tat protein was shown to induce cell death by apoptosis in a T cell line and in cultured peripheral blood mononuclear cells from uninfected donors. This Tat-induced apoptosis was inhibitable by growth factors and was associated with enhanced activation of cyclin-dependent kinases.

Apoptosis↗
PubMed1995

Prejunctional interaction of alpha 2-adrenoceptors and D2 dopamine receptors on perivascular sympathetic nerves.

1. Potential interaction between release-inhibiting prejunctional alpha 2-adrenoceptors and D2 dopamine receptors was investigated by measuring D2 receptor-mediated inhibition of stimulation-evoked tritium overflow from perfused rat tail arteries incubated with [3H]-noradrenaline. 2. In the presence of cocaine (10(-5)M), which enhanced stimulation-evoked tritium overflow, the D2 dopamine agonist N-0923 [(S)-(-) 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] (10(-8)M) was less effective at inhibiting stimulation-evoked tritium overflow compared to inhibition in the absence of cocaine. 3. In the presence of cocaine, yohimbine (10(-6)M) enhanced stimulation-evoked [3H]-noradrenaline release. Under these conditions, inhibition produced by N-0923 was enhanced compared to tissues without yohimbine. 4. In the presence of cocaine, the alpha 2-adrenoceptor agonist UK-14,304 (10(-7)M) reduced stimulation-evoked tritium overflow. However, in this case, N-0923-mediated inhibition was not significantly altered. 5. In most circumstances increasing or reducing activation of prejunctional alpha 2-adrenoceptors resulted in attenuation or enhancement, respectively, of D2 receptor activation. However, in the case of UK-14,304 this relationship did not hold. Thus, most but not all the evidence supports an interaction between prejunctional alpha 2-adrenoceptors and D2 dopamine receptors.

Adrenergic alpha-Agonists↗
PubMed1995

Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults.

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.

Acyclovir↗
PubMed1994

Bone marrow transplantation in Fanconi anemia using matched sibling donors.

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.

Abdomen↗
PubMed1994

Influence of age on control of norepinephrine release: Ca2+ channels and dopamine D2 receptors.

Possible age-related changes in the roles of L- and N-type Ca2+ channels and dopamine D2 receptors in control of norepinephrine release were investigated in tail arteries of F-344 rats. Nifedipine had no effect on stimulation-evoked tritium efflux at 6 or 24 months of age; however, omega-conotoxin GVIA reduced efflux by 70 to 80% at both ages even when frequency of stimulation was altered. Activation of prejunctional dopamine D2 receptors by the selective agonist N-0923 [(S)-(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +] inhibited contractile responses to transmural nerve stimulation in a frequency and concentration-dependent manner. Effects were similar from 6 to 26 months. Furthermore inhibition by N-0923 of stimulation-evoked [3H]norepinephrine efflux was not different at 12 and 24 months. Thus, N-type Ca2+ channels predominate in control of norepinephrine release, and this is unchanged with advancing age or stimulation intensity. Furthermore, D2 receptor-mediated inhibition of norepinephrine release is not altered with advancing age.

Aging↗
PubMed1994

Effect of calcium channel blockers on norepinephrine release and modulation by prejunctional D2 dopamine receptors.

Influx of calcium through voltage-dependent N-type calcium channels promotes the release of norepinephrine from nerve terminals. Contributions by L- and N-type calcium channels at different levels of nerve stimulation were examined in perfused rat tail arteries loaded with [3H]norepinephrine. Nifedipine had no effect while omega-conotoxin reduced tritium efflux by 69 to 82% depending on the stimulation intensity. Thus, N-type calcium channels predominated in the control of norepinephrine release, and the relative contribution of L- and N-type channels did not change when stimulation intensity was altered. We also explored the effect of calcium channel blockers on modulation of norepinephrine release by D2 dopamine receptors. Inhibition of stimulation-evoked tritium efflux by the D2 agonist N-0923 was similar in the absence and presence of nifedipine and/or omega-conotoxin. We conclude that D2 dopamine receptors are not coupled to L-type calcium channels; however, the role of N-type calcium channels requires further investigation.

Animals↗
PubMed1993

Maternal ethnicity and birthweight among blacks.

This paper examines the association of ethnicity and birthweight, adjusted for other maternal and infant characteristics, among black women who gave birth in Massachusetts from 1987 through 1989. Data are drawn from the standard certificate of live birth, which includes questions on race and ethnicity/ancestry as well as birthweight; maternal sociodemographic and biological characteristics; access to prenatal care; and infant characteristics. The study cohort consists of 18,571 black infants and a comparison group of 206,358 non-Hispanic white infants. Infants whose mothers reported their race as black were further categorized into six ethnic groups: American, Haitian, West Indian, Cape Verdean, Hispanic, and other black. In addition to descriptive analyses, we used multiple linear regression to measure the association between ethnicity, other characteristics, and birthweight; and we used multiple logistic regression to measure the odds ratio of low birthweight (ranging from 500 g to 2499 g) for the six black ethnic groups, adjusted for other characteristics. Results indicate that Americans have lower mean birthweight and generally higher levels of risk than other black ethnic groups. Compared to the reference group of non-Hispanic whites, Americans (OR = 1.49), other blacks (OR = 1.41), and West Indians (OR = 1.37) have significantly elevated relative risks of low birthweight.

Adult↗
PubMed1992

A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation.

BACKGROUND AND METHODS: Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a double-blind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. RESULTS: By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P less than 0.001). Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole (15.8 percent vs. 2.8 percent, P less than 0.001). Fluconazole prevented infection with all strains of candida except Candida krusei. Fluconazole was well tolerated, although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo. Although there was no significant difference in overall mortality between the groups, fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo (1 of 179 vs. 10 of 177, P less than 0.001). CONCLUSIONS: Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.

Bone Marrow Transplantation↗
PubMed1992

Complex prejunctional actions of the D2 dopamine agonists N-0923 and N-0924 in the rat tail artery.

In rat tail arteries preloaded with [3H]norepinephrine, the D2 dopamine receptor agonist N-0923 [(S)-(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +], (S)-(-)-enantiomer of N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin], inhibited tritium efflux and contractile responses evoked by nerve stimulation, indicating a prejunctional site of action. At higher concentrations (greater than or equal to 10(-7) M), N-0923 had additional effects which were blocked by the alpha-2 receptor antagonist yohimbine. In the presence of yohimbine, inhibition by N-0923 (10(-9) to 10(-6) M) of stimulation-evoked contractile responses correlated well with inhibition of tritium efflux, effects which were antagonized by sulpiride. The (R)-(+) enantiomer, N-0924 [(R)-(+)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +], also inhibited stimulation-evoked contractile responses (EC50 = 5.0 x 10(-7) M) and tritium efflux (EC50 = 6.0 x 10(-7) M) in the presence of yohimbine, but with reduced potency compared to N-0923 (EC50 = 4.0 x 10(-9) and 4.2 x 10(-9) M, respectively). At high concentrations (10(-6) M), both enantiomers also increased basal tritium efflux, an effect which coincided with contraction in the case of N-0923. The effect of N-0923 at the D2 receptor, measured as inhibition of stimulation-evoked contractile responses, was greatest when the intensity of stimulation was low (low frequency or short train lengths). When extracellular calcium was lowered to 1.0 mM, the inhibitory effect of N-0923 was increased whereas elevated calcium (5.0 mM) attenuated the action of N-0923.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Eccrine squamous syringometaplasia. A cutaneous sweat gland reaction in the histologic spectrum of 'chemotherapy-associated eccrine hidradenitis' and 'neutrophilic eccrine hidradenitis'.

A 31-year-old Hispanic man presented in the pancytopenic phase of acute myelocytic leukemia and was treated with the chemotherapeutic agents mitoxantrone and cytarabine. After 5 days, an erythematous, blanching, papular, crusted eruption developed on his forehead, chest, and legs. Some lesions showed confluence and all were at the same developmental stage. Clinical diagnoses included necrotizing vasculitis and sepsis. A biopsy specimen revealed widespread noninflammatory syringometaplasia of eccrine ducts. Well-developed intercellular bridges and eosinophilic cytoplasm were seen within the metaplastic cells; apoptoses and occasional mitoses were present. This process is distinct and probably occurred secondary to direct toxic injury from the chemotherapeutic drugs. Because similar changes have occurred in patients with neutrophilic eccrine hidradenitis, we believe our patient represents an example of the noninflammatory end of the spectrum of chemotherapeutic eccrine gland reactions.

Adult↗
PubMed1989

Prejunctional inhibitory effect of a dopamine D-2 agonist, N-0437, on vascular adrenergic responses.

N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin], a potent and selective agonist for D-2 dopamine receptors, was used to investigate inhibitory prejunctional dopamine receptors in the rat tail artery and rabbit ear artery. N-0437 inhibited contractile responses to transmural nerve stimulation in a frequency dependent manner. Thus, N-0437 profoundly inhibited responses to nerve stimulation in the rat tail artery at a frequency of 1 Hz (ED50 = 1.6 nM), but had minimal effects when nerves were stimulated at 6 Hz. The D-1/D-2 dopamine agonist, apomorphine, exhibited a similar frequency dependent inhibitory effect but with less potency (ED50 = 30 nM at 1 Hz). In concentrations up to 1 microM, N-0437 had no effect on responses to exogenously applied norepinephrine, but N-0437 inhibited [3H] norepinephrine efflux induced by transmural stimulation. Inhibitory effects of N-0437 were blocked by the D-2 antagonist sulpiride but not by the D-1 antagonist SCH 23390. Furthermore, the selective D-1 agonist SKF 38393 did not inhibit vascular responses to adrenergic nerve stimulation. These data indicate that the inhibitory effects of N-0437 are via activation of D-2 dopamine receptors that inhibit norepinephrine release. Thus, N-0437 shows potency and selectivity of action for prejunctional D-2 dopamine receptors in vascular tissues. The frequency dependence of the actions of N-0437 suggest that the level of sympathetic activity is an important variable in determining effectiveness of prejunctional modulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗