Biomedical subjects

N Lowe

Publications and source records attributed to N Lowe.

At least 19 recordsLinked to original sources

PubMed2000

Two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Humans↗

PubMed1999

The recognition of distorted DNA structures by HMG-D: a footprinting and molecular modelling study.

The high mobility group (HMG) domain is a DNA binding motif found in some eukaryotic chromosomal proteins and transcription factors. This domain binds in the minor groove of DNA inducing a sharp bend and also preferentially binds to certain distorted DNA structures. Although structures of sequence-specific HMG domains with their cognate double-helical DNA binding sites have been solved, the nature of the interaction of the domain with distorted DNA remains to be established. In this study we have investigated the interaction of HMG-D, a Drosophila counterpart of the vertebrate HMG1, with a DNA oligomer containing a bulge of two adenine residues. We show by footprinting that HMG-D binds preferentially on one side of the bulged DNA. Based on these data and on the published NMR structures of the HMG domain of HMG-D and the LEF-1-DNA complex, we modelled the HMG-D - bulged DNA complex. This model predicts that two residues, Val32 and Thr33, in the loop between alpha-helices I and II are inserted deep into the "hole" in the DNA formed by the two missing bases on one strand of the DNA bulge. Mutation of these residues confirmed that both are required for the efficient binding and bending of DNA by HMG-D. We discuss both the role of this loop in the recognition of distorted DNA structures by non-sequence specific HMG domain proteins and that of the basic tail in stabilising the induced DNA bend.

Amino Acid Sequence↗

PubMed1999

The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia.

BACKGROUND: Data suggest that androgenetic alopecia is a process dependent on dihydrotestosterone (DHT) and type 2 5alpha-reductase. Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with androgenetic alopecia. OBJECTIVE: We attempted to determine the effect of finasteride on scalp skin and serum androgens. METHODS: Men with androgenetic alopecia (N = 249) underwent scalp biopsies before and after receiving 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride or placebo for 42 days. RESULTS: Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively. CONCLUSION: In this study, doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels. These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg.

5-alpha Reductase Inhibitors↗

PubMed1999

Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.

BACKGROUND: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. OBJECTIVE: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. METHODS: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. RESULTS: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. CONCLUSION: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

5-alpha Reductase Inhibitors↗

PubMed1999

Effects of acitretin on the liver.

BACKGROUND: Therapy with aromatic retinoids for psoriasis is associated with abnormal liver function test findings and toxic hepatitis (in 1.5% of patients). OBJECTIVE: Our purpose was to determine the safety of acitretin with respect to liver function, on the basis of biopsy. METHODS: We treated 128 adults (with chronic, stable psoriasis) with oral acitretin (25-75 mg/day) for four 6-month intervals in a prospective, open-label, 2-year multicenter study. Liver biopsies were performed before and after study completion (2 years). RESULTS: Eighty-three available pairs of pretreatment and posttreatment liver biopsies demonstrated no change in 49 patients (59%), improvement in 20 (24%), and worsening in 14 (17%). Of these 14 patients with decrements in biopsy status, most changes were mild. There was no correlation between liver function test abnormalities or cumulative acitretin dose and changes in liver biopsy status. CONCLUSION: Acitretin therapy elicited no biopsy-proven hepatotoxicity in this prospective 2-year study. These findings suggest that periodic liver biopsy may not be necessary with acitretin treatment.

Acitretin↗

PubMed1998

Quality of life in patients with bioprostheses and mechanical prostheses. Evaluation of cohorts of patients aged 51 to 65 years at implantation.

BACKGROUND: The purpose of this study was 3-fold: to compare the quality of life (QOL) in age- and sex-matched patients who received biological and mechanical prosthetic valves in isolated aortic valve replacement, to compare the QOL of patients with aortic valve replacement with the general population, and to compare patients with biological and mechanical prostheses with certain valve-specific questions and relate these responses to overall QOL. METHODS AND RESULTS: Patient-perceived QOL was evaluated in 200 patients who were sampled from a population of 420 patients (age range 51 to 65 years) who underwent isolated aortic valve replacement in the period of 1986 to 1996. One hundred of the sampled patients had a mechanical valve inserted and an equal number had porcine bioprostheses. Three survey instruments were used to examine perceived QOL: the SF-12 form, a 7-valve specific question form, and the Lamy Smiley Faces form. The response to the questionnaires was 89.5% (179 patients). Patients with mechanical valves were more bothered by valve sounds (P < 0.01) and had a negative correlation (P < 0.01) between valve sound and QOL on the mental scale only. Patients with biological valves were more fearful of the need for reoperation (P < 0.01), but there was no correlation between fear and QOL. The mechanical valve group had a negative correlation (P < 0.01) between fear of reoperation and QOL on both the mental and physical scales. There was no difference between the 2 cohorts with respect to fear of valve failure. Patients with mechanical valves were more concerned about frequency of medical visits and blood tests (P < 0.01) as well as the possibility of anticoagulant-related bleeding events (P < 0.01). QOL was equivalent between the 2 groups and to the general population for the same age group. Ninety-seven percent of the patients indicated they would make the same surgical decision again with regard to valve replacement; there was no difference between the 2 valve groups on this question. CONCLUSIONS: Patient-perceived QOL is similar between patients with aortic mechanical and biological valve replacement in the studied age group and comparable to the general population of similar age. Although certain valve-specific differences exist between the 2 prosthetic types, these differences do not appear to affect overall QOL as described by these patients.

Aged↗

PubMed1998

Homozygous deletions at 3p12 in breast and lung cancer.

We have constructed a physical map of the region homozygously deleted in the U2020 cell line at 3p12, including the location of putative CpG islands. Adjacent to one of these islands, we have identified and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein. The DUTT1 gene is a member of the neural cell adhesion molecule family, although its widespread expression suggests it plays a less specialized role compared to other members of the family.

Breast Neoplasms↗

PubMed1998

Breastfeeding information and support services offered by Melbourne hospitals in antenatal classes.

Breastfeeding in industrialised societies is affected by a number of factors including antenatal class participation, timing of breastfeeding education, support networks available, and fathers' opinions. This study aimed to investigate the availability and type of breastfeeding information and support services offered by Melbourne hospitals. This was discussed in regard to the possible effect this may have on mothers' choice of feeding method. All hospitals known by Nursing Mothers' Association of Australia (NMAA) to be involved in obstetric care were asked to complete a questionnaire. Factors such as antenatal class timing, attendance, cost and content were investigated as indicators of the extent of services available. Specifically, services and information offered for women from non English speaking backgrounds (NESB) and from Aboriginal and Torres Strait Islands were identified. The study found that breastfeeding education is a small part of antenatal education in Melbourne hospitals. The inclusion of NMAA was widespread among hospitals, allowing access to information and support services. The amount of information and support services available for women from NESB and Aboriginal and Torres Strait Islander background needs to be expanded.

Breast Feeding↗

PubMed1998

What is an electronic patient record?

While organizations develop their Electronic Patient Records, there will be a transition period during which computerized and paper records will both exist, possibly on multiple clinical information systems. This paper describes a model that defines the patient system of record and its constituent paper elements and electronic components. The model has been adopted by a large academic health science center for their development of an electronic patient record. The model has clarified which systems and data constitute the patient system of record and the standards and policies that apply to these systems.

Academic Medical Centers↗

PubMed1997

A small conserved domain in the yeast Spa2p is necessary and sufficient for its polarized localization.

SPA2 encodes a yeast protein that is one of the first proteins to localize to sites of polarized growth, such as the shmoo tip and the incipient bud. The dynamics and requirements for Spa2p localization in living cells are examined using Spa2p green fluorescent protein fusions. Spa2p localizes to one edge of unbudded cells and subsequently is observable in the bud tip. Finally, during cytokinesis Spa2p is present as a ring at the mother-daughter bud neck. The bud emergence mutants bem1 and bem2 and mutants defective in the septins do not affect Spa2p localization to the bud tip. Strikingly, a small domain of Spa2p comprised of 150 amino acids is necessary and sufficient for localization to sites of polarized growth. This localization domain and the amino terminus of Spa2p are essential for its function in mating. Searching the yeast genome database revealed a previously uncharacterized protein which we name, Sph1p (a2p omolog), with significant homology to the localization domain and amino terminus of Spa2p. This protein also localizes to sites of polarized growth in budding and mating cells. SPH1, which is similar to SPA2, is required for bipolar budding and plays a role in shmoo formation. Overexpression of either Spa2p or Sph1p can block the localization of either protein fused to green fluorescent protein, suggesting that both Spa2p and Sph1p bind to and are localized by the same component. The identification of a 150-amino acid domain necessary and sufficient for localization of Spa2p to sites of polarized growth and the existence of this domain in another yeast protein Sph1p suggest that the early localization of these proteins may be mediated by a receptor that recognizes this small domain.

Amino Acid Sequence↗

PubMed1997

One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases. OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Administration, Topical↗

PubMed1997

Cyclosporine as maintenance therapy in patients with severe psoriasis.

BACKGROUND: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Administration, Oral↗

PubMed1995

Thioredoxin, a mediator of growth inhibition, maps to 9q31.

The human thioredoxin gene has been provisionally mapped to 3p11-p12. Recently thioredoxin cDNA has been isolated in a procedure that detects transcripts coding for growth-suppressing proteins, and thus the chromosomal location of the gene is of particular interest. Chromosome 3 is believed to harbor several tumor suppressor genes important in the development of lung and other common epithelial tumors. To establish more firmly the chromosomal location of the human thioredoxin gene, a somatic hybrid panel was used; it identified chromosome 9 as the location of the transcribed thioredoxin gene. Fluorescence in situ hybridization of a YAC encoding the transcribed thioredoxin gene refined the localization to 9q31.

Animals↗

PubMed1995

Efficacy and pharmacokinetics of two formulations of cyclosporine A in patients with psoriasis.

The efficacy and pharmacokinetic profiles of two oral formulations of cyclosporine A (Sandimmune and Neoral; Sandoz Pharmaceuticals, East Hanover, NJ) were evaluated in 37 patients with moderate to severe plaque psoriasis in a randomized, double-blind, modified, crossover study. Cyclosporine A (150 mg twice daily), administered in either formulation, reduced the severity of plaque lesions: 94% of all patients reported at least moderate improvement and 70% reported complete clearing. Approximately 2 weeks of therapy were required for drug exposure to stabilize on either formulation. Cyclosporine A exposure from Neoral was significantly greater relative to that from Sandimmune across all study weeks. At the eighth week (before crossover), AUC and Cmax values for Neoral and Sandimmune were 5618 +/- 1705 versus 3202 +/- 596 ng.h/mL and 1283 +/- 337 versus 623 +/- 173 ng/mL, respectively. In crossover analysis at steady state, the relative oral bioavailability of cyclosporine from the Neoral formulation was 54% greater than that from Sandimmune. Some pharmacokinetic parameters showed less variability both between and within groups of patients taking Neoral versus Sandimmune. Both formulations were well tolerated, in that most adverse events were of mild severity.

Chemistry, Pharmaceutical↗

PubMed1995

The safety of etretinate as long-term therapy for psoriasis: results of the etretinate follow-up study.

BACKGROUND: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy. OBJECTIVE: We assessed the safety of long-term therapy with etretinate for psoriasis. METHODS: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation to the frequency of these events in control populations. RESULTS: Our data do not provide evidence for an increased risk of cardiovascular disease, cancer, diabetes, or inflammatory bowel disease in association with long-term etretinate use. Although some patients reported that joint problems improved with the use of etretinate, a greater number associated the use of etretinate with joint problems. CONCLUSION: With proper patient selection and monitoring, long-term etretinate therapy (up to 4 years) does not appear to be accompanied by a substantial increased risk of major adverse effects.

Adult↗

PubMed1995

Chromosome specific paints from a high resolution flow karyotype of the mouse.

Chromosomes from antigen stimulated B-cells from spleens of inbred mice have been separated using flow cytometry into 18 distinguishable peaks. Using locus-specific oligonucleotides and fluorescence in situ hybridization to banded metaphase spreads, 15 individual chromosomes were identified: 1, 2, 3, 6, 7, 8, 9, 11, 12, 16, 17, 18, 19, X and Y. The remaining six chromosomes, occurring as pairs in three peaks, 4 with 5, 10 with 13, and 14 with 15, were resolved by flow sorting chromosomes from mice carrying an appropriate homozygous translocation and 4, 5 and 14 have been isolated in this way. This is the first demonstration of how a complete set of mouse chromosome paints can be produced.

Animals↗

PubMed1995

Laser skin resurfacing with the SilkTouch flashscanner for facial rhytides.

BACKGROUND: Effective treatment of facial rhytides has been reported using carbon dioxide (CO2) lasers with high peak power and short exposure time which creates char-free ablation. Char-free ablation can also be created using a Silktouch flashscanner attached to a conventional CO2 laser. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of the SilkTouch flashscanner in skin resurfacing. METHODS: The SilkTouch flashscanner attached to one of two continuous wave CO2 lasers was used to treat facial rhytides on 40 patients. Histopathology to evaluate the depth of penetration of the scanner on both CO2 lasers was performed on preauricular skin prior to excision during facelift surgery. Silicone surface replicas were obtained pre- and 2 months post-laser treatment on two patients and evaluated by optical micrometry. Clinical evaluation of all patients pre- and post-laser treatment was performed. RESULTS: Clinical evaluation showed significant improvement of facial rhytides. Optical micrometry revealed a decrease in rhytide volume, indicating rhytide improvement. CONCLUSION: The Silktouch flashscanner is effective for the treatment of facial rhytides.

Anesthesia↗

PubMed1995

Mini-slit graft hair transplantation using the Ultrapulse carbon dioxide laser handpiece.

BACKGROUND: The new Ultrapulse carbon dioxide (CO2) laser technology has added a new dimension to many cosmetic surgery procedures including hair transplantation. Early reports by Unger and David (Laser Hair Transplantation. J Dermatol Surg Oncol 1994;20:515-21) have been encouraging with the potential of minimal bleeding, ease of placing transplanted grafts, and an overall shortened operative time. A 2-mm slit handpiece has been recently created to expedite this procedure. OBJECTIVE: The purpose of this study is to further investigate the use and efficiency of the new Ultrapulse CO2 laser slit handpiece in hair transplants. METHOD: Mini-slit graft hair transplants using the new Ultrapulse CO2 laser slit handpiece were done on 25 patients in 30 transplant sessions. Donor minigrafts were obtained by the strip harvesting technique using a triple-blade scalpel. Approximately 200-400 recipient slits were made with the 2-mm slit handpiece at the laser setting of 350 mJ, 12 W, 0.8 seconds per pulse. RESULTS: All grafts were easily placed into recipient sites with minimal bleeding and charring. The procedure was done in half the time of the conventional non-laser technique. Postoperatively, patients were quite satisfied with little pain and swelling. Histologic exams of the laser-treated slits showed minimal adjacent tissue necrosis. Long-term follow-up visits showed good regrowth of hair in these grafts. CONCLUSION: The new Ultrapulse CO2 laser slit handpiece proved to be an effective tool for mini-slit graft hair transplantation.

Adult↗