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Biomedical subjects

M Lecha

Publications and source records attributed to M Lecha.

At least 19 recordsLinked to original sources
PubMed2006

Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation.

Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients.

Adolescent↗
PubMed2006

Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection.

BACKGROUND: First, to establish the mutations of the protoporphyrinogen-oxidase (PPOX) gene in four Spanish patients with variegate porphyria (VP). Second, study of carrier status detection in the families, including a four-generation Balearic family. Third, evaluation of the results of carrier detection screening methods. DESIGN: Blood samples of four patients and of 139 members belonging to four families, including four generations of a Balearic family were processed for mutation analysis of the 13 exons of PPOX gene. Biochemical studies were performed together (blood and faecal porphyrin analysis) and plasma fluorescence scanning for 626 nm peak emission detection. A questionnaire regarding clinical manifestations was submitted to all family members studied. RESULTS: Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077-1082insC: exon 10, and IVS6+2T-->A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checked in the carriers detected and found as not relevant or not present. Only 11 members of the 19 mutation-bearing individuals showed plasma fluorescence PV peak positivity. CONCLUSION: Demonstration of gene mutation is the most reliable means of detecting carriers in studies of variegate porphyria families. DNA analysis is the most sensitive carrier detection method and also allows transmission behaviour of the genetic defect to be established in successive generations of the affected families.

Adult↗
PubMed2005

Tacalcitol in the treatment of psoriasis vulgaris: the Spanish experience.

BACKGROUND: A group of vitamin D derivatives has revealed to be an efficient treatment for psoriasis. Different types of studies have been designed to confirm the efficacy of its use without relevant side-effects. OBJECTIVE: Evaluation of tolerability and efficacy of tacalcitol ointment in moderate psoriasis. DESIGN: A 2-month multicentre prospective open-label observational study in patients with psoriasis treated with tacalcitol ointment. METHODS: A cohort of patients with psoriasis vulgaris seeking medical advice and being treated with tacalcitol based on the decision of their dermatologists was selected. A 2-month follow-up was performed to assess efficacy and tolerability of tacalcitol in an ointment formulation (4 microg/g) once daily. A psoriatic lesion was selected in each patient in order to assess clinical symptoms (erythema, desquamation and thickness) by means of five-point scale: 0 (none) to 4 (maximal severity). Percentages of involved skin, adverse effects, physicians' global assessments of efficacy and tolerability, and patients' global satisfaction scores were also evaluated after 15-30 days (first visit) and 2 months (second visit) of treatment. RESULTS: A total of 556 patients were included. Mean psoriasis duration was 10.1 years (range, 0-61 years). Follow-up data were available for 493 patients in first follow-up visit and 449 in second (final) visit. Adverse events were uncommon (1.0% and 0.6% of patients in first and second follow-up visits, respectively). At first follow-up visit, mean decrease in selected lesions surface area (from a baseline value of 185.8 cm(2) per lesion) was 11.1 cm(2) (95% CI, 1.6-20.6; P = 0.0213). After 2 months of treatment, mean scores for erythema, desquamation and thickness changed from 2.2 +/- 0.8 to 1.1 +/- 0.8 (19% of patients with no erythema at final visit); from 2.4 +/- 0.8 to 0.6 +/- 0.7 (55% of patients with no desquamation); and from 2.2 +/- 0.9 to 0.8 +/- 0.6 (51% of patients with less thickness), respectively. Mean percentage of total body skin involvement was 14% (7.5% and 6.9% of anterior and posterior body surface, respectively). After 2 months of treatment, a 3.2% (95% CI, 2.7-3.8; P = 0.0001) and 3.0% (95% CI, 2.4-3.6; P = 0.0001) decrease was observed in the percentage of involved anterior and posterior skin surface area, respectively. Efficacy and tolerability evaluation by investigators was very good or good in 94% and 74% of patients, respectively; 78% of patients evaluated study treatment as satisfactory/very satisfactory. More than 80%, 50-80% and less than 50% of prescribed doses were used by 88%, 9.3% and 2.3% of patients, respectively. CONCLUSIONS: Tacalcitol was highly effective in the symptomatic treatment of moderate psoriasis. Compliance was very high, probably due to the easy and convenient application. Physicians' global assessments of tacalcitol were excellent, both for tolerability and efficacy. Excellent tolerability was confirmed by the low rate of adverse events. Our results in an everyday clinical setting show that tacalcitol is a useful therapy in patients with moderate psoriasis.

Administration, Cutaneous↗
PubMed2005

Epidemiology and clinical classification of onychomycosis.

OBJECTIVES: To review recent data - what is new in the epidemiology of onychomycoses? To identify the most relevant diagnostic criteria for effective therapy. METHODS: The preliminary results of the European Onychomycosis Observatory (EUROO) study were analysed. In this international study, physicians completed questionnaires concerning patient profile and the disease. RESULTS: One of the most interesting novel findings was that sampling requests were often not made [only 3.4% of general physicians (GPs) and 39.6% of dermatologists]. This means that no information about causative agent(s) was available, hindering appropriate treatment choice. Furthermore, contrary to previous findings, 70.7% of participants did not practice sports. Lastly, these preliminary findings showed that treatment strategy depends largely on the type of treating physician, with GPs preferring monotherapy and dermatologists preferring combination therapy. CONCLUSIONS: A consensus was reached that treatment strategy should depend on the severity of nail involvement and the causative fungus. It is thus important to promote the importance of sampling. To simplify the choice of an appropriate treatment, onychomycosis may be divided into just two clinical groups: onychomycosis with and without nail matrix area involvement. However, the distinct clinical findings (number and type of affected nails, multimorbidity, drug interaction, etc.) in each individual case must be taken into account to ensure an appropriate treatment decision.

Antifungal Agents↗
PubMed2005

Treatment options--development of consensus guidelines.

BACKGROUND: There are currently three main treatment strategies for onychomycosis: topical, oral and combination. Amorolfine nail lacquer appears to be the most effective form of topical monotherapy. However, the best mycological and clinical cure rates are obtained with combination therapy. Combination therapy increases antifungal spectrum, fungicidal activity and safety. New antifungals (triazoles and echinocandins) were recently developed, enabling new protocols. OBJECTIVES: To review available therapies. To design an algorithm for the management of onychomycoses in daily practice. RESULTS: Therapeutic choice should be based on numerous factors including patient's age and health, aetiology, extent of involvement and clinical form. The consensus was that topical monotherapy is recommended when < 50% of the nail is affected without matrix area involvement. Oral monotherapy or combination therapy is indicated when > 50% of the nail, including the matrix area, is involved. Topical treatments should not be used alone when topical drug transport is suboptimal (i.e. when dermatophytoma, onycholysis or spikes are present). Chemical or mechanical removal should also be considered whenever applicable (interruption of drug transport). CONCLUSION: In conclusion, treatment decision-making tools (e.g. an illustrated booklet or CD-ROM presenting each type of onychomycosis and criteria to be considered before selecting treatment regimen) would be valuable supports for the successful treatment of onychomycoses.

Administration, Oral↗
PubMed2004

Photopatch testing: a consensus methodology for Europe.

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

Dermatitis, Photoallergic↗
PubMed2004

Efficacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial.

BACKGROUND: A two-compound product containing calcipotriol 50 microg/g and betamethasone dipropionate 0.5 mg/g (Daivobet, Dovobet) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris. OBJECTIVE: To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris. METHODS: 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 microg/g once daily, or to tacalcitol 4 microg/g once daily. RESULTS: Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both). CONCLUSION: A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.

Administration, Topical↗
PubMed2003

Diagnosis and treatment of the hepatic porphyrias.

Porphyrias are a peculiar group of diseases resulting from hereditary or acquired partial deficiencies in seven of the eight enzymes in the biosynthetic pathway of heme. Biosynthesis of heme takes place in the erythropoietic system or in the hepatic tissue. Depending on the main location of the enzyme defect, porphyrias can be classified as erythropoietic or hepatic. There are seven basic clinical forms of porphyria related to a deficiency of each of the involved enzymes. Clinical manifestations in porphyria may be neurovisceral or cutaneous. Patients may present with acute attacks (acute porphyrias), cutaneous lesions (cutaneous porphyrias), or both (mixed porphyrias). Study of patients supected of having porphyria should include several steps: 1) clinical evaluation, 2) biochemical study, which enables us to classify the patient to a specific form of porphyria, followed if possible by 3) enzymatic assay(s), and 4) genetic studies to confirm an enzyme deficiency and its level and the causal genetic mutation. Unfortunately no curative treatment is available for any of the porphyrias. However, symptomatic treatments are available and are discussed in this article.

Acute Disease↗
PubMed2002

Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus.

BACKGROUND: Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. The disease is the result of a profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait, whereas familial porphyria cutanea tarda is dominant. At least 30 different mutations of the UROD gene have been identified in patients with HEP and familial porphyria cutanea tarda, with 1 predominant missense mutation (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with HEP. OBSERVATION: A 5-year-old patient with first-degree-related parents presented with HEP and mild symptomatology. We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were healthy carriers of the mutation. The mother had reduced UROD activity (50% of normal), whereas the father had normal UROD activity. Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. When the mother started a new pregnancy, a prenatal study showed the absence of F46L mutation in the fetus and no accumulation of porphyrins in the amniotic fluid. CONCLUSIONS: A new mutation in the UROD gene causes a mild HEP phenotype. A normal UROD enzymatic activity was observed in the father, despite the presence of the heterozygous mutation. To our knowledge, this observation is the first description of a prenatal exclusion of HEP.

Amino Acid Substitution↗
PubMed2001

Morphoea in three siblings.

Atrophoderma of Pasini and Pierini (APP) is an uncommon form of localized morphoea that occurs as superficial, hyperpigmented plaques distributed mainly on the trunk and proximal part of the limbs. There is little information about the influence of genetic and environmental factors on disease susceptibility and expression for localized scleroderma, although APP familial cases have been reported. We report three siblings without a family history of autoimmune disease presenting cutaneous lesions suggesting morphoea (APP variant).

Adult↗
PubMed2001

Idiopathic photodermatoses: clinical, diagnostic and therapeutic aspects.

UNLABELLED: Idiopathic photodermatoses are a group of photosensitivity dermatoses, which are not very frequent with the exception of polymorphous light eruption. Therefore, their recognition may not be easy for dermatologists who are not familiar with photosensitivity diseases. LEARNING OBJECTIVE: The information in this review is intended for giving clinical, diagnostic and therapeutic clues for the correct management of patients. Clinical features will be described together with diagnostic relevant procedures and usual therapeutic measures.

Chronic Disease↗
PubMed2001

Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain.

OBJECTIVE: In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy. PATIENTS/METHODS: A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group 1-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed. RESULTS: At week 12, mycological cure was attained in 42 of 45 patients (93.3%) in group AI-6, 29 of 35 patients (82.9%) in group AI-12, and 14 of 34 patients in group 1-12. The difference between both combination groups and the control group were significant (P < 0.001). The global cure rate at week 24 was 83.7% (36 patients) in group AI-6, 93.9% (31 patients) in group AI-12, and 68.8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant (P < 0.05). CONCLUSIONS: These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.

Administration, Oral↗
PubMed2000

[Influence of highly active antiretroviral therapy on the evolution of AIDS-associated Kaposi's sarcoma].

BACKGROUND: To evaluate the highly active antiretroviral therapy (HAART) in the Kaposi's sarcoma evolution. PATIENTS AND METHOD: Retrospective analysis of a cohort of 126 HIV infected patients suffering from Kaposi's sarcoma with or without HAART. Clinical evolution, immunological status (CD4+ cell count) and response to therapy (HIV-RNA plasma viral load and human herpes-8 virus determination). RESULTS: All patients without HAART died and the cumulate probability survival (SD) among those who received HAART was 2.078 (74) days. The CD4+ count at baseline in the HAART group was 130 (125) * 106/l and the HIV-RNA viral load was 196,818 (244,195) copies/ml while at the moment of the clinical response was 235 (209) * 106/l CD4 + and 2,629 (6.444) copies/ml, respectively. CONCLUSION: HAART prolongs survival in HIV patients suffering from Kaposi's sarcoma. There is a clear relationship among clinical response, HAART and immunological recovery.

Adult↗
PubMed2000

Large deletions of chromosome 9p in cutaneous malignant melanoma identify patients with a high risk of developing metastases. Hospital Clinic Malignant Melanoma Group, University of Barcelona.

Cutaneous malignant melanoma (CMM) is an aggressive tumour with a high metastatic potential. Deletions of chromosome 9p have been detected in CMM, some of which involve the CDKN2A/p14ARF genes. Loss of heterozygosity (LOH) of 16 microsatellite markers on 9p and mutations in the CDKN2A/p14ARF genes had been previously studied in 32 melanoma patients by our group. 9p deletions were detected in 15 primary tumours (45.5%) and are here correlated with the clinical outcome over 5 years and compared with classical prognostic factors. Eight of the 32 patients developed metastases (25%). The metastases were all detected within 768 days of the initial diagnosis. The patients without metastases were last monitored at least 1621 days after diagnosis. None of the 21 patients with more than eight microsatellites conserved developed metastases, whereas all of the eight patients who developed metastases had eight or more markers deleted. The sensitivity of this analysis to predict metastases was 100% (specificity 84%), whereas the sensitivity for the same sample using a Breslow thickness > 3 mm was 62.5% (specificity 68%). LOH of eight or more of the 9p microsatellite markers is therefore a useful prognostic factor to predict the development of metastases in the first 4.4-6.3 years (1621-2294 days).

Chromosome Deletion↗
PubMed1999

Urinary porphyrin excretion in a human population highly exposed to hexachlorobenzene.

BACKGROUND: Data from an epidemic reported in Turkey (1955-1959) is the only information about the relationship between hexachlorobenzene (HCB) intake and porphyria cutanea tarda in humans. No information is available on the HCB threshold exposure level to induce porphyria cutanea tarda. OBJECTIVES: To study HCB serum levels and urinary porphyrin excretion in the inhabitants of a village located near an organochlorine compound factory with high HCB concentrations in the air and to detect possible alterations in urinary porphyrin excretion and examine their relationship with HCB serum levels. DESIGN: Cross-sectional study. SETTING: Unit of Porphyrias of a tertiary care facility in Barcelona, Spain. PARTICIPANTS: Six hundred four inhabitants of the village who were older than 14 years provided serum and urine samples (185 participants were factory workers). MAIN OUTCOME MEASURES: Serum HCB was analyzed by gas chromatography coupled to electron capture detection. Quantification of urinary total porphyrins was performed by spectrofluorimetry. Porphyrin profile was determined by high-pressure liquid chromatography. RESULTS: Hexachlorobenzene was detected in all serum samples (mean, 39.8 ng/mL; range, 1.1-1616.0 ng/mL), and levels were higher in factory workers. Mean +/- SD level urinary total porphyrin average concentration was 98 +/- 69 nmol/L (range, 9-1009 nmol/L). Only the urine sample with the highest porphyrin concentration showed an increase of highly carboxylated porphyrins, with a typical profile of porphyria cutanea tarda. In the remaining 603 urine samples, coproporphyrin was the predominant fraction. CONCLUSION: The airborne exposure to and increased body burden of HCB in the Flix village population are not enough to trigger a significant alteration of the heme biosynthesis pathway.

Adolescent↗