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D Hoffman

Publications and source records attributed to D Hoffman.

At least 19 recordsLinked to original sources

The dbMHC microsatellite portal: a public resource for the storage and display of MHC microsatellite information.

Major histocompatibility complex (MHC) region Microsatellites (Msat) have been extensively used in various applications, such as disease mapping, forensics, and population genetics. A comprehensive review of HLA Msat primers has been previously published based on literature and sequence analysis, but electronic tools are lacking to make it easily accessible and actually used by the community. We have integrated data from this review, with an overlapping set of 31 Msat markers used in the 13th International Histocompatibility and Immunogenetics Workshop (IHIWS) to create a public archive that will synchronize published descriptions to a common framework. http://www.ncbi.nlm.nih.gov/projects/mhc. Currently, the dbMHC contains 389 primer pairs across the extended MHC targeting 281 distinct repeat regions (approximately 1/45 kb). Literature review and analysis of the primers reveal that over 200 synonymous names have been published for these markers. Users may view or download specific Msat data sets using the portal. Query options include name or partial name, primer sequence, neighboring genes, and/or position. Query results include locus name(s), a graphic showing of the relative location of the marker in relation to the classical HLA genes, a listing of the constituent primer pairs and name, a link to UniSTS, aliases, allele range (bp), overlapping single nucleotide polymorphisms, a link to e-polymerase chain reaction, and physical mapping information. To increase the utility of this resource, researchers using Msat markers in the HLA region are encouraged by the authors to submit new primers to the dbMHC. The minimal Msat submission consists of primers sequences, a submitter's name and contact information. Additional information recommended but not required is the laboratory protocol(s), known allele size range (bp), known aliases, and an exemplar sequence. Assigned UniSTS numbers can be used for primer pair standard identification.

Animals↗

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Adult↗

Comparison of two peri-wound skin protectants in venous leg ulcers: a randomised controlled trial.

OBJECTIVE: A randomised controlled trial was designed to determine whether or not early intervention with a suitable skin barrier preparation could prevent skin breakdown. This study was conducted to compare the efficacy and cost-effectivenss of two skin protectants, Cavilon No Sting Barrier Film (NSBF) (3M Health Care) and zinc paste compound, in the management of maceration and irritation of the peri-wound area of venous leg ulcers. METHOD: Thirty-five patients with venous leg ulcers and surrounding skin problems were randomised to receive either NSBF or zinc paste compound. The preparation was then applied at each dressing change for 12 weeks. All patients had been receiving compression bandaging before entering the study and continued wearing it throughout the 12-week study period. RESULTS: The decrease in wound area was 5.11+/-8.39cm2 in the NSBF group and 4.59+/-5.83cm2 in the zinc paste group. The healing rate was 0.046cm per week with NSBF and 0.039cm per week with zinc paste. There was a significant difference in the time required to remove and re-apply the skin protectants: an average of 0.19 (+/-0.17) minutes in the NSBF group and 5.53 (+/-2.10) minutes in the zinc paste group (p<0.0001). CONCLUSION: Both products were effective barrier preparations. However, NSBF was easy to apply and transparent. The zinc paste was messy to apply and difficult to remove, and thus took up considerably more nursing time than NSBF. DECLARATION OF INTEREST: This study was supported by 3M Health Care.

Aged↗

Predictors of antiretroviral adherence.

This study was conducted in order to help determine the key factors that predict adherence to antiretroviral medications. A total of 115 HIV/AIDS patients who were having trouble adhering to their antiretroviral regimens completed face-to-face interviews in which adherence levels, medication side effects, mental health, social support, patient-provider relationship characteristics, substance use and health anxiety were assessed. Three measures of adherence were used: adherence over the past three days, adherence over the past week, and adherence over the past month. Logistic regression analyses indicated strongest prediction of three-day adherence, with mental health, social support, patient-provider relationship characteristics and side effects contributing to prediction. Past week adherence was associated with age and social support measures, and showed a marginal association with side effects. Past month adherence was less strongly predicted, with social support and alcohol use contributing to prediction. Thus, a variety of factors were found to determine adherence, and implications of the findings for adherence models and interventions are discussed.

Adolescent↗

Outcomes of bleb excision and conjunctival advancement for leaking or hypotonous eyes after glaucoma filtering surgery.

AIM: To determine outcomes of bleb excision and conjunctival advancement for leaking or hypotonous eyes after glaucoma filtering surgery. METHODS: In a retrospective case series the medical records of all patients who underwent bleb excision and conjunctival advancement surgery for bleb leaks or hypotony (defined as IOP less than 6 mm Hg, associated with reduced vision) at the Jules Stein Eye Institute and the Yale University Eye Center between January 1993 and June 2002 were reviewed. Only patients with more than 6 months of follow up were included. Complete success was defined as resolution of the pre-existing leak or hypotony, with maintenance of IOP > or =6 and < or =21 mm Hg, in the absence of further glaucoma surgery and without any glaucoma medication. Qualified success met the above criteria with or without the use of glaucoma medications. Success rates were analysed with Kaplan-Meier survival curves. RESULTS: 49 eyes were included in the study; 13 eyes had overt bleb leaks, 27 eyes had hypotony. Nineteen patients underwent resuturing of sclera and/or placement of a pericardial graft in addition to bleb excision and conjunctival advancement. Mean preoperative IOP increased from 3.2 (SD 2.4) mm Hg (range 0-10 mm Hg) to 13.8 (4.8) mm Hg (range 6-29 mm Hg) at last follow up (p<0.0001). Mean preoperative visual acuity improved from 0.6 (0.3) logMAR (range 0-2) to 0.3 (0.3) logMAR (range 0-2) at final follow up (p<0.0001). 16 eyes (40%) were classified as complete success and 17 additional eyes achieved qualified success, for a total of 33 eyes (83%) achieving at least qualified success. There was no significant difference in the rate of complete success (p = 0.95) or qualified success (p = 0.88) between the group of patients who underwent bleb excision and conjunctival advancement alone versus those who also had resuturing of sclera and/or placement of a pericardial graft. Failures included three eyes that had persistent hypotony without leak, requiring additional bleb revision, and four with uncontrolled IOP, two of whom underwent additional glaucoma surgery. CONCLUSION: Bleb excision with conjunctival advancement is a successful procedure for bleb repair. This technique provides successful resolution of leaks and hypotony, maintains glaucoma control with or without medication, and preserves vision with minimal postoperative complications in a majority of eyes.

Adult↗

Barriers and successful strategies to antiretroviral adherence among HIV-infected monolingual Spanish-speaking patients.

Focus groups were conducted with HIV-infected, monolingual Spanish-speaking patients (N = 81) taking antiretrovirals in order to: (1) determine what barriers impede medication adherence; (2) determine what strategies facilitate adherence; and (3) investigate the health care provider-patient relationship and whether it impacts adherence. Both quantitative and qualitative information was gathered. Participants were prescribed an average of 11 pills per day (M = 11.4, SD = 7.0, range = 1-30). Only 32% of participants were consistently adherent when self-report of medication taking (yesterday, the day before yesterday, and last Saturday) was compared to prescribed regimen. The most frequently reported strategies were: learning more about the medications (77%), accepting the need to take them (75%) and refilling prescriptions early or on time (70%). Barriers most often reported were: feeling depressed or overwhelmed (21%), simply forgetting (19%) and sleeping through a dose (17%). From the qualitative data, four main issues emerged: patient characteristics, the health care professional-patient relationship, language and cultural barriers within the health care system, and the medication regimen. Among this Latino sample, having someone to live for was extremely important in terms of patient adherence. Language barriers were reported, and the use of translators was not always seen as a sufficient remedy. Differences between monolingual Spanish-speaking patients' and English-speaking patients' strategies and barriers are discussed.

Adult↗

On-chip definition of picolitre sample injection plugs for miniaturised liquid chromatography.

The fabrication of components for a miniaturised liquid chromatography system on silicon has recently been reported by our research group [J. Cap. Electrophoresis Microchip Technol. 6 (1999) 33; Analyst 125 (2000) 25]. To date, inlet and outlet connection ports, separation micro-channels (20-200 microm in width, 0.5-10 microm in depth, 15-60 cm in length), and an intersection for picolitre injection have been etched on a silicon wafer and then sealed with a Pyrex cover plate on which platinum electrodes for on-chip detection have been patterned. The platinum electrodes have been used for the amperometric detection of phenol, using 20 nl off-chip injection. In this work we present our latest results obtained with on-chip pressure driven picolitre injection, designed to realize the full capabilities of this micro-LC system. The injection volume is dependent on the micro-channel depth, width, and also on the intersection length, allowing injection in the low nanolitre to picolitre range.

Chromatography, High Pressure Liquid↗

Five novel RPGR mutations in families with X-linked retinitis pigmentosa.

X-linked forms of retinitis pigmentosa (XLRP) are among the most severe because of their early onset, often leading to significant visual impairment before the fourth decade. RP3, genetically localized at Xp21.1, accounts for 70% of XLRP in different populations. The RPGR (Retinitis Pigmentosa GTPase Regulator) gene that was isolated from the RP3 region is mutated in 20% of North American families with XLRP. From mutation analysis of 27 independent XLRP families, we have identified five novel RPGR mutations in 5 of the families (160delA, 789 A>T, IVS8+1 G>C, 1147insT and 1366 G>A). One of these mutations was detected in a family from Chile. Hum Mutat 17:151, 2001.

Carrier Proteins↗

Homeless mothers with severe mental illnesses and their children: predictors of family reunification.

Although many homeless women lose physical custody of children, prior studies have not examined predictors of reunification. To explore factors associated with separation and potential resources for reunification, baseline data from 1,542 homeless women with mental illness were used to identify unique characteristics of separated mothers. Separated mothers demonstrated greater vulnerabilities than accompanied mothers did, but more resources than women who are not mothers did. Of 698 separated mothers, 118 (17%) were reunited with children at 12 months. Changes in housing, psychosis, substance use and therapeutic relationships predicted reunification. Results suggest that programs for homeless mothers with severe mental illness can affect changes that promote family reunification.

Adolescent↗

trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents.

The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D(2) and D(4) receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dichlorophenyl)piperazine (5m) and (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D(2) and D(4) receptors and had a D(2)/D(4) ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.

Animals↗

Relationship between structural abnormalities and short-wavelength perimetric defects in eyes at risk of glaucoma.

PURPOSE: To determine the relative prevalence of blue-yellow perimetric defects and structural abnormalities of the optic nerve and nerve fiber layer in eyes at risk of glaucoma. METHODS: Seventy-two eyes (of 72 patients) at risk of glaucoma, with normal white-on-white full threshold perimetry, were examined prospectively with blue-yellow full-threshold perimetry (Humphrey). Structural evaluations were conducted with qualitative assessment of stereoscopic color optic disk photographs and monochromatic nerve fiber layer photographs performed independently by three masked examiners (a glaucoma specialist and two glaucoma fellows), and statistical analysis of summary parameters was obtained with scanning confocal laser tomography (abnormal defined as values outside 95% confidence limits established in normal control subjects). RESULTS: Kappa values for interobserver agreement were 0.64, 0.88, and 0.79 for optic disk evaluation and 0.59, 0.60, and 0.61 for nerve fiber layer evaluation. Thirteen (18%) of 72 eyes had blue-yellow abnormalities. A total of 30 eyes (42%) were identified as having a structural abnormality; 29 (40%) had qualitatively determined optic disk abnormalities, 21 (29%) had qualitatively determined nerve fiber layer defects, and 26 (36%) had statistically significant structural abnormalities. Twelve of 13 eyes with blue-yellow defects had a detectable structural abnormality; all 12 had abnormalities identified with disk photography, nine with nerve fiber layer photography, and 12 by scanning laser tomography. CONCLUSIONS: Clinically detectable structural abnormalities frequently coexist with blue-yellow perimetric defects in patients with ocular hypertension. A substantial proportion of patients with ocular hypertension with normal blue-yellow perimetry has early detectable glaucomatous structural abnormalities.

Glaucoma, Open-Angle↗

Barriers to antiretroviral adherence among HIV-infected adults.

Success of highly active antiretroviral therapies (HAART) relies on HIV-infected patients being able to adhere to complicated treatment regimens for extremely long periods of time. Four focus groups with patients taking antiretrovirals (N = 39) were conducted to: (1) determine what strategies facilitate successful adherence; (2) determine what barriers prevent adherence; and (3) investigate the health-care provider and patient relationship and how it may impact adherence. Quantitative and qualitative information was gathered. Participants were prescribed an average of 15 pills per day (M = 14.7, SD = 6.3, range 4 to 36). Findings from the quantitative data revealed that the three strategies used most often to aid adherence were: carrying special containers for medication; having a health-care provider explain or clarify medication requirements; and carrying food and water for adherence to special instructions. The most difficult barriers for patients were sleeping through dose time, problems in following special instructions, and changes in daily routines. From the qualitative data, four main categories of barriers and aids to adherence emerged: patient characteristics, the health-care provider-patient relationship, the health-care system, and issues related to the medication regimen. Barriers related to the health care provider-patient relationship included patient satisfaction with their provider, as well as quality of communication with the provider. In addition, health-care system barriers caused difficulty in maintaining adherence. Implications for patient as well as provider interventions are discussed.

Adult↗

Assessment of anxiety and depression in young children: support for two separate constructs.

Validated the interrelatedness of depression and anxiety in young children by testing four latent factor models: dual construct, unrelated; dual construct, correlated; single construct; and second-order or higher order analysis to test that depression and anxiety are primary constructs under the higher order factor of general affective distress. Children (N = 86) were ages 6 to 11, with mothers who were HIV-symptomatic or diagnosed with AIDS. Depression and anxiety measures included the Children's Depression Inventory (Kovacs, 1992), selected items from the Dominic-R (Valla, Bergeron, Berube, Gaudet, & St-Georges, 1994), and the Revised Children's Manifest Anxiety Scale (Reynolds & Richmond, 1985). Structural equation modeling was used to test the models. Model 2 (dual construct, correlated) fit the data better than did Models 1 and 3; results for the higher order model were identical to Model 2, suggesting the higher order model is equivalent to the dual-construct model.

Anxiety Disorders↗

Permeability and absorption of leuprolide from various intestinal regions in rabbits and rats.

The in vitro permeability and in vivo absorption of leuprolide in different intestinal regions were measured to investigate the feasibility for site-specific delivery of leuprolide in the gastrointestinal (GI) tract. In vitro permeability of leuprolide in the rabbit GI tract was performed using a side-by-side diffusion apparatus and the permeability coefficients in the jejunum, ileum and colon were 0.27x10(-7), 2.96x10(-7) and 7.85x10(-7)cm/s, respectively. Varying the donor drug concentrations from 2 to 10 mg/ml, the permeability coefficients were independent of the donor concentration, suggesting the transport mechanism of passive diffusion. Using an intestine loop model in anesthetized rats, bioavailabilities of leuprolide in the jejunum, ileum and colon were 1.28, 5.62 and 9.59%, respectively. Drug recovery from the loop 5 h after dosing was 10.7% in jejunum, 24.5% in ileum and 40.7% in colon. Additional in vivo studies using conscious rats showed that the bioavailability of leuprolide was less than 1% for both ileal and colonic administration. In vivo absorption of leuprolide from ileum was not significantly different from colon in conscious rats. Sodium salicylate, a permeation enhancer, was co-administered with leuprolide to the rat ascending colon, and results showed a 4-fold increase in the bioavailability in conscious rats. Thus, in vivo studies indicate that both absorption and enzymatic degradation of leuprolide in the GI tract is site-dependent and the lower intestine may be an advantageous region for oral delivery of leuprolide.

Animals↗