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PubMed2006

Complications of body sculpture: prevention and treatment.

In many countries, lipoplasty is the most frequently performed aesthetic procedure. It has been promoted as a safe, easy-to-learn, outpatient procedure. Although plastic surgeons have developed safety measures to perform the technique, there are serious risks, including death at a rate of 1/5000 procedures. Life-threatening complications include pulmonary embolism, hemorrhage, perforation, infection, lidocaine toxicity, epinephrine toxicity, third space fluid shifts, and fat embolism syndrome. Aesthetic complications include undercorrection (insufficient fat removal), overcorrection (excess fat removal), irregular fat removal with palpable and visible irregularities, edema, hematoma, seroma, local infection, cutaneous slough, hyperpigmentation, vasculopathies, and permanent color changes in the skin. In this article we present methods to prevent and, when possible, treat these complications.

Anesthetics, Local↗

PubMed2005

Melanin in the trabecular meshwork is associated with age, POAG but not Latanoprost treatment. A masked morphometric study.

We wished to conduct a light and electron microscopic investigation of pigmentation within the trabecular meshwork of normals and primary open angle glaucoma (POAG) patients. In particular we wished to get a precise determination of whether there was a relationship between pigmentation and age. In addition we wanted to know if there was a difference between normals and POAGs and whether trabecular meshwork hyperpigmentation was associated with topical latanoprost medication. A total of 25 sham trabeculectomies conducted on post mortem donor eyes provided the age-matched normals and there were 62 trabeculectomy specimens from POAG patients. These were masked and the meshwork subjected to qualitative and quantitative morphological investigation. Light and electron microscopy confirmed that most of the trabecular meshwork melanin was phagocytosed and within meshwork cells. The granules were measured and found to be of the large iris epithelial type. Light microscopic morphometric analysis showed that the number of meshwork cell profiles that contained melanin increased both in normals and POAGs with age. However there was nearly three times more pigmented meshwork cells in the POAGs than the normals. The POAGs were divided into three groups of (1) minimal or no medication prior to surgery, (2) maximal medical therapy and (3) maximum medical therapy including latanoprost (12 specimens). All groups were significantly greater that the normals but of the three it was the maximal medical therapy group (without latanoprost) that had the highest pigmentation. We concluded that pigmentation of the meshwork is age-related and it is elevated in POAG by mechanisms unknown. The melanin accumulation seems to be partly due to the disease process, partly as a consequence of chronic antiglaucoma medication but interestingly not due to latanoprost even in patients where there is iris darkening (four specimens).

Administration, Topical↗

PubMed2006

Addison's disease presenting as male infertility.

OBJECTIVE: To present a case of primary male infertility with severe oligospermia and hyperpigmented skin as the main presenting clinical signs. DESIGN: Case report. SETTING: University-affiliated teaching hospital. PATIENT(S): A 32-year-old male with severe oligospermia and his 31-year-old female partner with normal cycles. INTERVENTION(S): Hydrocortisone, fludrocortisone, methimazole, and eventual IVF. MAIN OUTCOME MEASURE(S): Improved semen analysis, correction of Addison's disease, correction of hyperthyroidism, and ART pregnancy. RESULT(S): Severe oligospermia of 5 million per milliliter with 15% motility and ACTH level of 2,800 pg/mL on presentation. Endocrinology evaluation revealed cortisol of <0.1 microg/dL, and Cortrosyn test showed no response (Addison's disease). The patient was incidentally found to have a thyroid stimulating hormone level of <0.1 microIU/mL, T4 of 9.5 microg/dL, Free T4 Index calculation of 11.6 microg/dL, and quantitative triiodothyronine of 273 ng/dL on presentation. His Addison's disease was managed with hydrocortisone and fludrocortisone, and his hyperthyroidism, with methimazole. Semen parameters increased to 34 million per milliliter with 45% motility and 5% Kruger morphology 1 year after initial presentation. Hormone parameters normalized. Rather than allowing for more time for natural conception or IUI, the couple decided to proceed with IVF because of insurance coverage before semen parameters normalized. CONCLUSION(S): This is the first reported case of Addison's disease presenting as male infertility with hyperpigmentation of the skin being the only other presenting sign. The underlying etiology of the Addison's in this case remains uncertain, but it is presumed because of autoimmunity. Addison's disease may be associated with hyperthyroidism, and hyperthyroidism may have contributed to the oligospermia. This case highlights why men with abnormal semen parameters should be thoroughly evaluated before proceeding with assisted reproduction.

Addison Disease↗

PubMed2004

Tattoo removal among Ethiopian Jews in Israel: tradition faces technology.

BACKGROUND: Many Jews in Ethiopia adopted the Christian custom of tattooing various parts of the body, either after conversion or to hide their Jewish origin. After emigrating to Israel, they sought to remove these foreign symbols to better blend with society. The aim of this study was to describe the use of laser technology for tattoo removal in a high-risk dark-skinned population and to highlight one way in which the interaction of modern medical communities with people from developing countries can open new avenues of research. PATIENTS AND METHODS: The study sample consisted of 401 women and 3 men of Ethiopian origin with Fitzpatrick skin type V or VI. Ages ranged from 15 to 53 years. All tattoos were blue/black and had been made by injecting charcoal into the skin. Most (n = 392, 97%) were located on the forehead or the forehead and temples (n = 312); 69% were cross-shaped. Patients underwent 3 to 6 laser treatments (average 3.6) with the Q-switched Nd:YAG (n = 380, 94%) or ruby (n = 24) laser at intervals of at least 8 weeks. The percent of clearing was scored by two independent investigators as follows: 1 = 0%-25%; 2 = 26%-50%; 3 = 51%-75%; 4 = 75%-100%. Pigmentary and textural changes were classified as none, mild, moderate, or severe. The duration of follow-up after the last treatment was 6-8 months. RESULTS: At the last follow-up, the clearance score was 4 in 92% of the patients and 3 in the remainder. Transient (2-4 months) mild hyperpigmentation was noted in 177 (44%) patients, and mild textural changes in two, both treated with the Q-switched laser. There were no cases of scarring or permanent pigmentary changes. CONCLUSION: Laser removal of carbon-based tattoos in an Ethiopian population yielded an excellent to good aesthetic outcome with no complications, similar to results in light-skinned patients. These findings have important implications for improving the quality of life of Ethiopian immigrants in Israel.

Adolescent↗

PubMed2005

Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study.

BACKGROUND: The treatment of keloids remains unsatisfactory. Intralesional 5-fluorouracil (FU) has not been much investigated as a monotherapy in the treatment of keloids. OBJECTIVE: We sought to evaluate the use of intralesional injections of 5-FU in the treatment of keloids. METHODS: A total of 20 patients (11 male and 9 female) were treated once weekly with intralesional injections of 5-FU (50 mg/mL). Patients received an average of 7 treatments. Average injection volumes were 0.2 to 0.4 mL/cm2. All patients had full blood cell count, liver function tests, and renal function tests before and after treatment was commenced. A total of 10 patients had biopsy specimens taken before starting treatment as a baseline and after 6 sessions. Routine hematoxylin-eosin and immunohistochemical analysis detecting Ki-67 and transforming growth factor-beta were performed on paraffin sections. All patients were followed up for 12 months, or until recurrence was noted. RESULTS: Of 20 patients, 17 (85%) showed more than 50% improvement. Only one did not respond favorably. Small and previously untreated lesions improved the most. Pain (20 of 20), hyperpigmentation (20 of 20), and tissue sloughing (6 of 20) were the main adverse effects. Histopathologic and immunohistochemical evaluation were consistent with the clinical observations. Ki-67 proliferative index was significantly reduced (P = .0001) after treatment. Transforming growth factor-beta was reduced less significantly. Recurrence was noted in 47% (9 of 19) of patients who responded to treatment within 1 year. A correlation was found ( P = .028) between the duration of the lesions and recurrence. CONCLUSION: Our study demonstrates that intralesional 5-FU may be effective in the treatment of keloids, but recurrence is common and further investigation is required.

Adolescent↗

PubMed2005

Lymphangioma circumscriptum: treatment with hypertonic saline sclerotherapy.

A 38-year-old woman came for treatment of multiple clear vesicles and hemorrhagic papules on the posterior aspect of the right shoulder and the right axillary vault of 5 years' duration. These lesions would spontaneously manifest as clear or blood-filled vesicles (or both) and appear to be exacerbated by physical contact from certain articles of clothing. A biopsy was done and the results revealed lymphangioma circumscriptum. The purpose of this case study was to evaluate a new form of treatment of lymphangioma circumscriptum with the use of 23.4% hypertonic saline sclerotherapy. The patient's lymphangioma circumscriptum significantly resolved with minimal side effects, such as mild hyperpigmentation. Decreased sensitivity was noted and no further treatment was indicated. This case showed that hypertonic saline 23.4% solution can be effective in treating the appearance of vesicles containing clear fluid or lymph and those containing red blood cells in superficial lymphangiomas and that this treatment can be considered for long-term management of lymphangioma circumscriptum.

Adjuvants, Immunologic↗

PubMed2006

Concomitant treatment of psoriasis of the hands and feet with pulsed dye laser and topical calcipotriol, salicylic acid, or both: a prospective open study in 41 patients.

BACKGROUND: Psoriasis of the hands and feet is a chronic disease which is often resistant to the usual topical therapies. It has considerable morbidity and seriously affects the quality of life of patients. OBJECTIVE: We sought to prospectively evaluate the efficacy and safety of pulsed dye laser (PDL) treatment of psoriasis of the hands and feet. METHODS: In all, 41 patients with therapy-resistant psoriasis of the hands and feet were treated once every 4 to 6 weeks with PDL at 585-nm wavelength, 450-microsecond pulse duration, 7-mm spot diameter, and 5- to 6.5-J/cm2 fluence. Calcipotriol ointment and salicylic acid 5% to 10% ointment were used as keratolytic agents. Treatment efficacy was evaluated by blinded comparison of photographs of the lesions taken before and after PDL treatment in each patient. RESULTS: A good to very good improvement in the lesions was observed in 76% of the patients after treatment. An average duration of remission was 11 months. Side effects were transient purpura, moderate discomfort during the treatment, transient hyperpigmentation or hypopigmentation, and incidental transient crustae. LIMITATIONS: This was an open prospective study with a limited number of patients who were concomitantly treated with calcipotriol and salicylic acid ointment. Patients with photointolerance, on medication with phototoxic or photoallergic drugs, and with widespread psoriasis were excluded. CONCLUSIONS: Concomitant treatment with PDL and topical calcipotriol, salicylic acid, or both was a satisfactory modality for treating psoriasis of the hands and feet. There was a subjective improvement in the symptoms and quality of life in all patients.

Adolescent↗

PubMed2006

Nephrogenic fibrosing dermopathy: a series in a non-Western population.

BACKGROUND: Nephrogenic fibrosing dermopathy (NFD) is a newly proposed clinical entity resembling scleromyxedema. This is mainly found in patients with chronic renal failure who have undergone hemodialysis. Nearly all cases have been reported in the Western population. OBJECTIVE: We sought to assess whether NFD cases occurred in a non-Western population and to ascertain the frequency, clinical characteristics, histopathology, and natural history of the condition in the event of its occurrence. METHODS: Patients postdialysis in the nephrology department of a tertiary referral hospital in Kolkata, India, were evaluated clinically and histopathologic assessment was done on the basis of a clinical scoring to ascertain the frequency of the condition and its characteristics. This report is based on the findings of the first 3 years of an ongoing study. RESULTS: NFD was diagnosed in 6 of 2146 patients postdialysis 0.28%). In transplant recipients undergoing dialysis, NFD was diagnosed in 2 of 43 patients (4.65%). The average number of dialyses undergone by the patients was 7.2 (range: 2-16). Of the 6 cases of NFD, 5 conformed to the diagnosis of chronic kidney disease-V. Among them, 3 were noninsulin-dependent diabetes mellitus and one each were cases of chronic glomerulonephritis and systemic lupus erythematosus. One case followed dialysis in acute tubular necrosis. All cases clinically showed circumscribed thickening, roughened texture, hardening, xerosis, and infiltrated papules, plaques, or both. One case showed rippled pigmentation, four showed varied hyperpigmentation, two demonstrated localized fibrosis, and one resembled papular mucinosis. Increased thickness of dermis, increased number of plump spindle cells, abundance of thick collagen bundles with prominent clefts, and sparse small, multinucleated histiocytes were the hallmark of microscopic findings. LIMITATIONS: The inherent nature of the study precluded the inclusion of NFD cases without any background of dialysis, which have now been reported. No statistical conclusions may be established from our small series. CONCLUSION: To our knowledge, this is the first reported series of NFD outside North America and Europe.

Acute Kidney Injury↗

PubMed2006

Evaluation of the treatment of port-wine stains with the 595-nm long pulsed dye laser: a large prospective study in adult Japanese patients.

BACKGROUND: Treatments of port-wine stains with conventional pulsed dye laser yield inconsistent results. OBJECTIVE: We evaluated the efficacy and safety of the longer pulse duration 595-nm dye laser. METHODS: Sixty-six adult Japanese patients were enrolled in this prospective study. The laser treatment with a cooling device was repeated 4 times at 8-week intervals with a consistent setting of 10-ms pulse duration and an energy fluence of 12 J/cm2, using 7-mm spot size. RESULTS: Improvement of port-wine stains was observed after multiple treatments, and 67% of the patients achieved either good or excellent response after the fourth treatment. Transient purpura, edema, or both were noted immediately after each treatment (76%-79% and 58%-67%, respectively). Hyperpigmentation (8%-17%) and hypopigmentation (6%-14%) were also mild and their occurrence did not increase by repeating treatments. LIMITATIONS: Eighty five percent of the patients were classified as having Fitzpatrick skin type IV. CONCLUSION: Our study indicated that the 595-nm dye laser with 10-ms pulse duration may be effective and well tolerated in the treatment of port-wine stains in adult Asians.

Adult↗

PubMed2006

Anterior segment imaging using optical coherence tomography and ultrasound biomicroscopy in secondary pigmentary glaucoma associated with in-the-bag intraocular lens.

A 43-year-old man with high myopia developed unilateral pigmentary glaucoma with recurrent episodes of painless blurred vision in the left eye following uneventful phacoemulsification. Bilateral cataract surgery was performed with capsular bag implantation of a +4.00 diopter AcrySof MA60 intraocular lens (IOL) (Alcon Laboratories) followed by a neodymium:YAG laser capsulotomy. Secondary iatrogenic dispersion syndrome in the left eye with subsequent intraocular pressure elevation was suspected in the presence of anterior chamber pigmented cells, circular epithelial iris loss around the pupil, and trabecular hyperpigmentation. Close contact between the edge of the IOL and the posterior pigmented iris epithelium, which was clinically suggested by anterior biomicroscopy, was documented by ultrasound biomicroscopy and optical coherence tomography of the anterior segment.

Adult↗

PubMed2006

Betamethasone cream for the treatment of pre-pubertal labial adhesions.

PURPOSE: We evaluated the efficacy of 0.05% betamethasone cream for the treatment of pre-pubertal labial adhesions. METHODS: We retrospectively reviewed the records of 19 children with labial adhesions who were treated with betamethasone cream from 6/2001 to 3/2003. Children were treated with 1 to 3 courses of twice-daily 0.05% betamethasone cream for 4 to 6 weeks. Successful lysis of adhesions was assessed by clinical exam or parental phone contact and outcomes were defined as: (1) success--complete separation of labia, (2) partial success--greater than 75% separation, (3) progression to surgical lysis, and (4) lost to follow-up. RESULTS: Nineteen patients with an average age of 58 months (range 12 to 132 months) were treated. Four of the 19 patients had never been treated previously and 1 had been treated previously with surgical lysis of adhesions only. Fourteen of the 19 patients had been previously treated with conjugated estrogen (Premarin) cream. Two of these fourteen patients had also undergone surgical lysis of adhesions. Severity of adhesions ranged from 33% to 99% labial closure. Betamethasone cream was successful in treating 13/19 (68%) pre-pubertal labial adhesions. Eleven (85%) of these 13 patients had complete resolution of labial adhesions with 1 course of treatment, 1 (7.5%) had resolution with 2 courses of treatment and 1 (7.5%) had resolution with 3 courses of treatment. One patient had a partial success with 3 courses of betamethasone cream. Two (11%) patients underwent surgical lysis of adhesion after 1 and 2 courses of betamethasone cream respectively. Three (16%) patients were lost to follow-up. Average follow-up was 7 months (range 1-24 months). No adverse outcomes or untoward effects were noted in any of the patients treated. CONCLUSIONS: Betamethasone 0.05% cream appears to be a safe and effective treatment of pre-pubertal labial adhesions as primary therapy or in patients that have failed previous therapies and it may avoid the undesirable side effects of breast budding and hyperpigmentation that can be associated with Estrogen creams.

Administration, Topical↗

PubMed2005

Radiation recall dermatitis with pemetrexed.

Pemetrexed has recently been approved for use in combination with cisplatin as first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation therapy is frequently administered to the thoracic orifices and no data are available about the interactions between radiotherapy and pemetrexed. We report the first case of radiation recall dermatitis occurring after pemetrexed chemotherapy in a patient with MPM previously treated with radiation therapy to the thoracoscopy and drainage orifices. The patient received chemotherapy with pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy delivering 21 gray in 3 days. Conventional premedication by folic acid and intramuscular administration of Vitamin B12 and prednisolone was correctly performed. Twelve days later, confluent erythematous and pruritus rash of the irradiated skin was observed. The toxicity grade of this lesion was evaluated at 2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the Radiation Therapy Oncology Group. Pemetrexed challenge was performed without worsening of skin lesions. Three weeks later, skin cicatrisation was observed after a desquamative phase. Persistent hyperpigmentation was seen in the irradiated skin. Pemetrexed could also act as a radiosensitizing agent that should be used with care for several weeks after radiotherapy.

Aged↗

PubMed2004

The neurofibromatoses: hereditary predisposition to multiple peripheral nerve tumors.

Neurosurgeons must be aware of the neuro-fibromatoses because they frequently present with nervous system tumors. Such patients develop numerous peripheral nerve sheath tumors; fortunately, only a few of these tumors are symptomatic or malignant. The tumor burden in individual patients can be remarkable, however, producing significant morbidity and requiring extensive or repeated care by a skilled neurosurgeon. Because it is impossible to predict which of the deep neurofibromas will undergo malignant transformation, it behooves clinicians and patients to be aware of any change in symptoms or growth of tumors, because early resection of MPNST offers the only chance for cure. Neurosurgical professionals should be familiar with the diagnostic criteria of the neurofibromatoses, because the patient who presents with an initial neurofibroma or schwannoma immediately falls into a category in which those disorders must be ruled out. In this regard, a family history of nerve sheath tumors is revealing and should prompt referral for a clinical genetics evaluation. Cutaneous manifestations of NFI can confirm the diagnosis at initial presentation. Missing the initial presentation of a patient with NF2 can lead to marked morbidity, such as deafness,because surveillance for subsequent tumors was inadequate. Tumorigenesis in all neurofibromatoses involves loss of tumor suppressor genes. These disorders illustrate that the two-hit loss of tumor suppressor gene model, which applies best for NF2, is oversimplified. As with most cancers,a theory of multistep progressive acquisition of genetic changes that promote unregulated grow this emerging in schwannomatosis. In addition, the hyperpigmentation and learning disability of NF 1 highlight that loss of one copy of the gene is sufficient to cause nontumoral manifestations of the disorder. Genetic counseling and testing have an important role in the diagnosis of NFI and NF2 as well as in the management of all the neurofibromatoses.

Genetic Predisposition to Disease↗

PubMed2004

What is lost by digitizing stereoscopic fundus color slides for macular grading in age-related maculopathy and degeneration?

OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN: Comparative observational case series. PARTICIPANTS: Twenty-five patients (50 eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least 1 eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral United Kingdom population. Retinal photography was performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on Ektachrome slide transparency film. The images were centered on the macula. The color transparencies were then digitized. The grading process has been set up based on the International ARM Epidemiology Study Group. All images were independently graded by 3 retinal specialists. Both kappa statistics and exact agreement were calculated to assess agreement between and within observers and between the 2 master copies derived from the gradings of the color slides and digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies derived from the gradings obtained from stereoscopic slide transparencies and digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93% (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was 94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93% (kappa, 0.78) for the area covered. For the presence of choroidal neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was 95% (kappa, 0.83) for the area covered. For individual features of CNV, exact agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and 2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because of the close agreement for most categories between the grading of stereoscopic color slides and digitized images, digitized nonstereoscopic color images prove to be useful for grading ARM and AMD.

Diagnostic Techniques, Ophthalmological↗

PubMed2005

Tyrosinase inhibitory lignans from the methanol extract of the roots of Vitex negundo Linn. and their structure-activity relationship.

Phytochemical investigation of the methanol extract of Vitex negundo afforded eight lignans; negundin A 1, negundin B 2, 6-hydroxy-4-(4-hydroxy-3-methoxy)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaledehyde 3, vitrofolal E 4, (+)-lyoniresinol 5, (+)-lyoniresinol-3alpha-O-beta-d-glucoside 6, (+)-(-)-pinoresinol 7, and (+)-diasyringaresinol 8. The structures of these compounds were elucidated unambiguously by spectroscopic methods including 1D and 2D NMR analysis and also by comparing experimental data with literature data. The tyrosinase inhibitory potency of these compounds has been evaluated and attempts to justify their structure-activity relationships have been made in the present work. The compound 5 was found to be the most potent (IC(50)=3.21 microM) while other compounds demonstrated moderate to potent inhibitions. It was found that the substitution of functional group(s) at C-2 and C-3 positions and the presence of the -CH(2)OH group plays a vital role in the potency of the compounds. The compound 5 can act as a potential lead molecule to develop new drugs for the treatment of hyperpigmentation associated with the high production of melanocytes.

Inhibitory Concentration 50↗

PubMed2004

Chalcones as potent tyrosinase inhibitors: the effect of hydroxyl positions and numbers.

The inhibition of tyrosinase is one of the major strategies to treat hyperpigmentation. Various limitations are associated with many of these inhibitors, such as high cytotoxicity, poor skin penetration and low stability in formulations. In continuation of our previous study [J. Agric. Food Chem. 51 (2003) 1201], showing that isoliquiritigenin chalcone (ILC) is a potent tyrosinase inhibitor, the present study aims to characterize the chalcone family as new tyrosinase inhibitors, and demonstrate their potential whitening potency. Nine mono-, di-, tri- and tetrahydroxychalcones were tested as inhibitors of tyrosinase mono- and diphenolase activities, showing that the most important factor in their efficacy is the location of the hydroxyl groups on both aromatic rings, with a significant preference to a 4-substituted B ring, rather than a substituted A ring. Neither the number of hydroxyls nor the presence of a catechol moiety on ring B correlated with increasing tyrosinase inhibition potency. 4-Hydroxychalcone (4-HC), ILC and Butein inhibited tyrosinase and shortened the lag period of enzyme monophenolase activity from about 490 min (control) to 30 min (ILC). As pigmentation also results from auto-oxidation, the antioxidant activity of 4-HC, ILC and Butein, were tested. Results showed that chalcones are also potent antioxidants, with Butein the most potent. We may conclude that chalcones are potentially potent new depigmentation agents, with their double effect of reduction and antioxidant activity. A deeper understanding of the relation between their structures to their potency will contribute to designing the optimal agents.

Antioxidants↗

PubMed2005

Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan.

Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.

Arsenic↗

PubMed2006

Severe outbreak of disease in the southern chamois (Rupicapra pyrenaica) associated with border disease virus infection.

An outbreak of a previously unreported disease affecting southern chamois (Rupicapra pyrenaica) in the central Pyrenees (NE Spain) was recorded in 2001 and 2002. There was a marked temporal distribution, most animals being found between February and June. After the outbreak, the population was found to have decreased by about 42%, most probably due to the disease. We examined 20 affected chamois. Clinical manifestations included depression, weakness and movement difficulties in all cases. Three chamois presented abnormal behaviour, with absence of flight reaction, and 16 showed different degrees of alopecia with skin hyperpigmentation. At necropsy cachexia was observed in all animals, four chamois had abscesses in different parts of the body, four had pneumonia, one had an extensive subcutaneous infection on the head and neck and one had severe orchitis. Microscopic lesions were found in the brain, mainly edema, gliosis, espongiosis, cariorrexis and neuronal multifocal necrosis. A perivascular mononuclear inflammatory infiltrate was present in three of them. Skin lesions included marked follicular atrophy, mild to moderate epidermal hyperplasia with orthokeratotic hyperkeratosis and follicular hyperkeratosis, and hypermelanosis. In 13 chamois there were haemosiderin deposits in the spleen, and in three individuals kidney "cloissone" was observed. Intraeritrocitic parasites were detected either by direct observation or PCR in 8 of 17 chamois. A pestivirus was isolated and detected by RT-PCR from 12 of 13 affected chamois and antigenic characterized as border disease virus by monoclonal antibodies. This is the first time a border disease virus has been associated with an outbreak of a high-mortality disease in a wild species.

Animals↗