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Biomedical subjects

A C Chu

Publications and source records attributed to A C Chu.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in photorejuvenation and inflammatory acne vulgaris.

BACKGROUND: Nonablative lasers are widely used for treatment of wrinkles, atrophic scars and acne. These lasers stimulate dermal remodelling and collagen production, but the early molecular stimulus for this is unknown. The mechanism of nonablative lasers in inflammatory acne is variously suggested to be damage either to sebaceous glands or to Propionibacterium acnes. Their effects on cytokine production are unknown. OBJECTIVES: To assess the in vivo effects of a short pulse duration nonablative pulsed-dye laser (NA-PDL) previously used for photorejuvenation and treatment of acne, on cytokine production, P. acnes colonization density and sebum excretion rate (SER). METHODS: We examined the effect of NA-PDL (NliteV; Chromogenex Light Technologies, Llanelli, U.K.) on P. acnes colonization before and after laser therapy using a scrub-wash technique and culture at 0 and 24 h (n = 15), on SER using absorptive tape at 0, 2, 4, 8 and 12 weeks (n = 19) and on cytokine mRNA using reverse transcription-polymerase chain reaction from skin biopsies at 0, 3 and 24 h (n = 8). Results NA-PDL had no effect on P. acnes or SER. Transforming growth factor (TGF)-beta1 mRNA increased fivefold after 24 h and 15-fold in two subjects (P = 0.012). CONCLUSIONS: TGF-beta is known to be a potent stimulus for neocollagenesis and a pivotal immunosuppressive cytokine which promotes inflammation resolution. Its upregulation by NA-PDL provides a possible unifying molecular mechanism linking stimulation of dermal remodelling in photorejuvenation with inhibition of inflammation in acne. Damage to P. acnes or sebaceous glands cannot explain the effect of this device in acne.

Acne Vulgaris↗
PubMed2006

Calcipotriol/betamethasone dipropionate for the treatment of psoriasis.

The two-compound product calcipotriol/betamethasone dipropionate is arising as a first-line treatment for mild-to-moderate plaque psoriasis. Its beneficial action is attributed to the synergistic effect of its components on keratinocyte proliferation and differentiation, and on inflammation. The good tolerability of the two-compound product is thought to be due to the anti-inflammatory effect of betamethasone. Evidence from short-term (4-12 weeks) and long-term use (> 1 year) has shown a good safety profile. Areas such as the face or skin folds, which are sensitive to the components of the combination, should be avoided. Finally, it is unsuitable for use in unstable psoriasis, in which potent steroids may lead to an increased inflammatory response.

Anti-Inflammatory Agents↗
PubMed2004

Treatment of xanthoma disseminatum with cyclophosphamide.

Xanthoma disseminatum is a rare non-Langerhans cell (class II) histiocytosis, which is often resistant to treatment. We describe an illustrative case with extensive mucocutaneous, ocular, laryngeal, pituitary and central nervous system involvement, which responded to treatment with cyclophosphamide. The presentation, course and treatment of the condition are reviewed. Many of the non-Langerhans cell histiocytoses represent a spectrum of diseases of dermal dendrocytes ranging from self-limiting and benign conditions to multisystem progressive diseases that respond poorly to treatment and severely impair quality of life. We suggest that chemotherapy should be considered at an early stage in the more aggressive subtypes of non-Langerhans cell histiocytoses.

Adolescent↗
PubMed2004

Safety and side effects of the acne drug, oral isotretinoin.

Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.

Abnormalities, Drug-Induced↗
PubMed2003

Pulsed-dye laser treatment for inflammatory acne vulgaris: randomised controlled trial.

BACKGROUND: Low-fluence (low irradiation energy density) pulsed-dye lasers (PDLs) have been used for atrophic acne scarring, and anecdotal experience suggests that long-term improvements in inflammatory acne can be seen after one PDL treatment. Our aim was to compare the efficacy and tolerability of such PDL treatment with sham treatment in patients with facial inflammatory acne in a double-blind, randomised controlled trial. METHODS: We recruited 41 adults with mild-to-moderate facial inflammatory acne. We randomly assigned patients to PDL (n=31) or sham treatment (n=10). Treatment was given at baseline and patients were seen after 2, 4, 8, and 12 weeks. Assessors and participants were unaware of treatment allocations. Primary outcome measures were acne severity after 12 weeks and adverse events at any time. Secondary measures were change in lesion counts after 12 weeks and change in acne severity with time. Analysis was by intention-to-treat. FINDINGS: After 12 weeks, acne severity (measured by Leeds revised grading system) was reduced from 3.8 (SD 1.5) to 1.9 (1.5) in the PDL group and 3.6 (1.8) to 3.5 (1.9) in the sham group (p=0.007). Treatment was well tolerated. Total lesion counts fell by 53% (IQR 19 to 64) in PDL patients and 9% (-16 to 38) in controls (p=0.023), and inflammatory lesion counts reduced by 49% (30 to 75) in PDL patients and 10% (-8 to 49) in controls (p=0.024). The most rapid improvements were seen in the first 4 weeks after treatment. INTERPRETATION: PDL therapy improves inflammatory facial acne 12 weeks after one treatment with no serious adverse effects.

Acne Vulgaris↗
PubMed2002

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

BACKGROUND: Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. OBJECTIVES: The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. METHODS: This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. RESULTS: There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). CONCLUSIONS: No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.

Adolescent↗
PubMed2002

A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.

BACKGROUND: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate. OBJECTIVE: To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris. METHODS: 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks. RESULTS: The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle). CONCLUSION: Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.

Administration, Topical↗
PubMed2001

Low density lipoprotein as a targeted carrier for doxorubicin in nude mice bearing human hepatoma HepG2 cells.

Doxorubicin (DOX) was coupled to human low density lipoprotein (LDL) to form a complex (LDL-DOX). When injected into mice, LDL-DOX was more accumulated in liver than free DOX. In contrast, LDL-DOX was less accumulated in heart than free DOX. In in vitro studies on human hepatoma (HepG2) cells, although the cellular uptake of LDL-DOX was higher than that of DOX, the anti-proliferative effect of LDL-DOX on these tumor cells was smaller than that of LDL. However, when LDL-DOX or DOX was administered to nude mice bearing HepG2 cells implanted on the shoulder, the anti-proliferative effects on the tumor cells of both drugs were similar. Histological analyses indicated that organization of myocardial filaments was disrupted and vacuolization was observed in DOX-treated group when compared with control group whereas LDL-DOX-treatment did not exhibit any damage in the host's heart. Enzymatic analyses also demonstrated that plasma lactate dehydrogenase activity, which is a common indicator of heart damage, was elevated in DOX-treated group when compared with control group whereas the activity of this enzyme was unchanged in LDL-DOX-treated group. The results in present study indicate that LDL can be used as a targeted carrier for DOX because LDL-DOX can exhibit similar anti-proliferative effect as DOX on tumor but reduce the DOX-induced cardiotoxicity in the host.

Animals↗
PubMed2001

Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo.

BACKGROUND: Recent advances in the pathophysiology of vitiligo have demonstrated defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may be involved in the regulation of melanin synthesis, and receptors for 1,25-dihydroxyvitamin D3 have been demonstrated on melanocytes. OBJECTIVES: We conducted an open study to determine the efficacy and tolerability of calcipotriol cream as monotherapy and in conjunction with psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. METHODS: Twenty-six patients with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and four were placed on combination treatment with twice-daily topical calcipotriol 50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly. RESULTS: Treatment was well tolerated at all sites and no adverse effects were reported. After a therapy time of 3-9 months (mean 6 months), 77% (17 of 22) of those treated with monotherapy showed 30-100% improvement, and three of the four patients on combination treatment showed good response. CONCLUSIONS: Topical calcipotriol appears to be an effective and well-tolerated treatment for vitiligo and can be safely used in conjunction with PUVA, but controlled studies are necessary to exclude the possibility of spontaneous repigmentation.

Adolescent↗
PubMed2001

The potential role of abnormal E-cadherin and alpha-, beta- and gamma-catenin immunoreactivity in the determination of the biological behaviour of keratoacanthoma.

BACKGROUND: Failure of E-cadherin and its associated proteins alpha-, beta- and gamma-catenin is believed to lead to disruption of cell-cell adhesion and to contribute to neoplasia. OBJECTIVES: To determine the pattern of E-cadherin and alpha-, beta- and gamma-catenin immunostaining in keratoacanthoma (KA) and to evaluate its potential value in routine histopathology in differentiating KA with benign from that with malignant biological behaviour. METHODS: We examined the expression of E-cadherin and alpha-, beta- and gamma-catenin in KA and correlated the histopathological features with the immunohistochemical findings. Next, we compared the immunohistochemical findings of KA with those found in malignant (squamous cell carcinoma, SCC) and benign (warts) lesions. In addition to the established histopathological criteria we used the Ki-67 index, a well-known marker of cell proliferation. Immunoperoxidase staining of E-cadherin and alpha-, beta- and gamma-catenin, and Ki-67 determination, were performed in paraffin-embedded sections of 12 KAs taken from archival material. On reviewing the histology, seven of the 12 KAs were characterized as 'classical' KA, and the rest as 'borderline' KA or KA resembling SCC. Additionally, 28 well, nine moderately and five poorly differentiated SCCs and 20 warts were examined. RESULTS: Most 'classical' KAs (79-86%) showed normal membranous immunostaining and a low Ki-67 index. The remaining 'classical' KAs showed abnormal expression, in a staining pattern resembling that of well-differentiated SCC. All 'borderline' KAs showed a high Ki-67 index (> 40%) and abnormal expression of the adhesion molecules studied, identical to that of poorly differentiated SCC. Expression of E-cadherin and alpha-, beta- and gamma-catenin was found to be more frequently abnormal in 'borderline' KA compared with that in 'classical' KA (P < 0.05). Among E-cadherin and alpha-, beta- and gamma-catenin expression and Ki-67 index, only the expression of beta-catenin was more frequently found to be abnormal in total SCC than in total KA (P < 0.05). Expression of E-cadherin and alpha-, beta- and gamma-catenin was more frequently found to be abnormal in well-differentiated SCC than in 'classical' KA (P < 0.05). In total, as well as in 'classical' or 'borderline' KA, an agreement between expression of E-cadherin and of catenins was seen. CONCLUSIONS: These findings suggest that E-cadherin and catenins may be very helpful in distinguishing between 'classical' and 'borderline' KA, as the expression of these adhesion molecules in 'classical' KA is identical to that found in normal epidermis, overlapping with well-differentiated SCC in some cases. In 'borderline' KA, expression of adhesion molecules is identical to that in poorly differentiated SCC.

Biomarkers↗
PubMed2001

Systemic B-cell lymphoma presenting as an isolated lesion on the ear.

We report a case of systemic B-cell lymphoma that presented as an isolated cutaneous lesion on the ear, mimicking a primary cutaneous B-cell lymphoma. Although there was no clinical evidence of systemic disease, bone marrow involvement was found on further investigation and subsequent immunoglobulin gene analysis revealed an identical clone in the skin lesion and bone marrow aspirate. Evidence of a t(14 : 18) translocation was not identified. This case is unusual for several reasons. First, involvement of the pinna as a presenting feature of systemic lymphoma has not been reported previously. Second, the cutaneous lesion had been present for 3 years prior to diagnosis and there has been no clinical progression of systemic lymphoma during 2 years of follow-up. Third, the lymphoma does not correspond exactly to any of the entities in the REAL classification of systemic B-cell lymphoma. This case underlines the indolent nature of some systemic B-cell lymphomas and the need to investigate thoroughly patients with disease apparently confined to the skin.

Antigens, CD↗
PubMed2001

Endemic (African) Kaposi's sarcoma presenting as a plantar tumour.

We present a case of the aggressive variant of African endemic Kaposi's Sarcoma (AKS) which presented as a large fungating and ulcerated plantar mass. Our patient responded extremely well to chemotherapy with no recurrence for 9 months after treatment completion. AKS is one of the most common cutaneous neoplasms in black Africans and although rare in Europe, it may be seen more frequently in the future because of the ease of international travel. The existing classification of KS into five different types (classic, African-endemic, iatrogenically immunocompromised patients, epidemic HIV-related and Mediterranean-endemic) cannot address fully the many anomalies described in the disease. The detection of a new herpes simplex-like viral DNA sequence (HHV-8) in different types of KS helps to explain some of the enigma described in this disease.

Aged↗
PubMed2001

Erythema gyratum repens and acquired ichthyosis associated with transitional cell carcinoma of the kidney.

Both erythema gyratum repens (EGR) and acquired ichthyosis are distinctive dermatoses which have strong associations with internal malignancy. EGR usually precedes the diagnosis of malignancy whereas acquired ichthyosis commonly manifests after the detection of malignancy. We report a patient who initially presented with a figurate eruption of EGR which later developed into a widespread ichthyosis with disappearance of the serpiginous rash. Further investigations revealed an underlying transitional cell carcinoma of the kidney, an association which has not previously been reported with either EGR or acquired ichthyosis. The occurrence of two paraneoplastic skin disorders in the same patient may be explained by tumour cell secretion of transforming growth factor alpha, which has been shown to be mitogenic for keratinocytes.

Aged↗
PubMed2000

Inhibition of P-glycoprotein expression and reversal of drug resistance of human hepatoma HepG2 cells by multidrug resistance gene (mdr1) antisense RNA.

The development of multiple drug resistance in tumor cells is a significant problem in cancer therapy. In human, one of the reasons causing the resistance is due to the overexpression of the mdr1 gene product, P-glycoprotein. In our study, we had developed multiple drug resistant HepG2 cell line (HepG2/DR). To reverse the resistance, HepG2-DR cells were treated with antisense RNA against mdr1 gene. Total RNA and protein were extracted from the transfected cells. Northern analysis showed that mRNA level of mdr1 was decreased whereas a reduction in P-glycoprotein was detected by Western blot. By using flow cytometry, the ability of intracellular doxorubicin retention increased and drug efflux decreased in the treated cells. The result also showed that the cellular sensitivity to doxorubicin, vincristine and methotrexate measured in IC50 increased 83.3% 84.6% and 50% respectively. All these findings suggested that the expression of p-glycoprotein was successfully inhibited by antisense RNA and the drug resistance was reduced.

ATP Binding Cassette Transporter, Subfamily B, Mem↗