FEBRUARY 2.003
FEBRERO 2.003
Data-Medicos
Dermagic/Express MEDermatology Journal
Febrero 2.003 February 2.003
1.) Massive
hepatocellular [correction of hepatocullular] necrosis: was it caused by
Orlistat? XENICAL
Med Sci Law 2002 Oct;42(4):309-12
Lau G, Chan CL.
Health Sciences Authority, Centre for Forensic Medicine, Singapore, Republic of
Singapore. [email protected]
Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in
conjunction with appropriate dietary control, for the treatment of obesity. It
is generally deemed to be a safe drug, which mainly exerts a topical action on
the stomach and small bowel, with negligible systemic absorption and oral
bioavailability. Consequently, its adverse effects have largely been limited to
relatively mild gastrointestinal disorders. However, there have been recent,
published reports of non-fatal acute hepatitis and systemic hypertension
associated with its use. The present case concerns a 62-year-old male who died
from massive hepatocellular necrosis, consistent with drug-induced, fulminant
hepatitis, associated with the use of oral orlistat, presumably administered at
the recommended daily dose of 360 mg. It is postulated that this may represent a
rare idiosyncratic reaction to the drug.
2.)
Alefacept (Biogen). (Amevive )
PSORIASIS
Curr Opin Investig Drugs 2001 May;2(5):631-4
Bashir SJ, Maibach HI.
Department of Dermatology, University of California, San Francisco 94143-0989,
USA. [email protected]
Alefacept (B-9273) is an LFA-3-Ig fusion protein CD2 antagonist under
development by Biogen for the potential treatment of autoimmune diseases,
including psoriasis and transplant rejection [270267]. It is in phase III trials
for psoriasis [349467]. In October 2000, the company reported that Amevive was
on track for regulatory filing in the second half of 2001 [385250], with a
possible launch in the second half of 2002 [395628]. The company began a pivotal
phase III trial in the US in December 1999, involving patients with chronic
plaque psoriasis [349467]. A second phase III trial has also been initiated
[362199], [374040]. Results from both trials are expected in mid-2001 [396544].
In April 2001, SalomonSmithBarney confirmed that a regulatory filing was
expected in Europe and the US in the second half of 2001 and stated that
alefacept would be critical to the future earnings growth of the company
[407796]. In June 1999, Merrill Lynch estimated product launch in 2001 [327145],
[344773]. Sales in 2001 and 2002 were anticipated to be US $20 million and US
$100 million, respectively [327145].
3.)
Medium-dose ultraviolet A1 therapy for pityriasis lichenoides et varioliformis
acuta and pityriasis lichenoides chronica.
J Am Acad Dermatol 2002 Sep;47(3):410-4
Pinton PC, Capezzera R, Zane C, De Panfilis G.
Department of Dermatology, Azienda Spedali Civili di Brescia, Brescia, Italy.
BACKGROUND: Ultraviolet A1 (340-400 nm) was found to be effective in the
treatment of cutaneous T-cell-mediated diseases. OBJECTIVE: The purpose of the
present study was to assess the efficacy of UVA1 phototherapy for pityriasis
lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica
(PLC). METHODS: Eight patients (3 with PLEVA and 5 with PLC) received 60 J/cm(2)
UVA1 daily until remission. Four patients also had lesions inaccessible to UVA1
that were used as control lesions. Immunocytologic studies of skin infiltrates
and circulating T cells were done. RESULTS: Six patients showed complete
clinical and histologic recovery. Two patients with PLC had a partial
improvement. Unirradiated control lesions never improved. Serious short-term
adverse effects were not encountered. No effects on circulating lymphocytes were
reported. CONCLUSION: UVA1 therapy is an effective and well-tolerated treatment
for PLEVA and PLC. The therapeutic activity seems to be related to direct
effects on cutaneous inflammatory infiltrates because the lesions in nonexposed
cutaneous areas did not respond.
4.)
Pimecrolimus identifies a common genomic anti-inflammatory profile, is
clinically highly effective in psoriasis and is well tolerated.
J Invest Dermatol 2002 Oct;119(4):876-87
Rappersberger K, Komar M, Ebelin ME, Scott G, Burtin P, Greig G, Kehren J,
Chibout SD, Cordier A, Holter W, Richter L, Oberbauer R, Stuetz A, Wolff K.
Department of Dermatology, Division of General Dermatology, University of
Vienna, A-1090 Vienna, Austria.
The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release
inhibitor that so far has not been administered systemically to humans. In this
phase I/II randomized double-blind, placebo-controlled, multiple rising dose
proof of concept study psoriasis patients were treated with oral pimecrolimus or
placebo. Gene profiling identified a common genomic profile with a
downregulation of genes associated with inflammation but no changes in gene
expression linked to drug-related side-effects. A steady state of pimecrolimus
was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per
ml and 589.9 ng h per ml, respectively, at steady state at the highest dose.
There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice
daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity
Index by 60% and 75%, respectively. Histopatho logically and
immunopathologically there was a reversion of the psoriatic phenotype towards
normal. There were no notable clinical, laboratory, kidney function, or
immunologic side-effects. We conclude that pimecrolimus taken orally is highly
effective in a concentration-dependent manner in patients with psoriasis and on
a short-term basis it is well tolerated and this is confirmed by its
pharmacogenomic profile. The latter also indicates that pimecrolimus should be
equally effective in other inflammatory skin diseases.
5.) Risk of breast
cancer in post-menopausal women using hormone replacement therapy.
J Med Assoc Thai 2002 May;85(5):583-9
Ratanawichitrasin A, Reansuwan W, Ratanawichitrasin S, Bhodhisuwan K,
Kongpatanakul S.
Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University,
Bangkok, Thailand.
OBJECTIVE: To study the relationship of hormone replacement therapy (HRT) in
post-menopausal women and risk of breast cancer. PATIENTS AND METHOD: The
authors conducted a case-control study comparing the proportion of HRT used
between breast cancer and non-breast-cancer women. Cases were breast cancer
patients who had natural menopause (excluded hysterectomy) and aged > or =
50-years-old from the Siriraj Breast Cancer database (1983-1996). Controls were
post-menopausal volunteers aged 50 year or older who visited Siriraj Hospital
for other purposes such as elderly clinics, health check, etc. After informed
consent, well-trained surgeons examined the women in the control group to
exclude any potential breast cancer. Patient characteristics and risk factors
were collected. RESULTS: Of 1,913 patients in the database, 623 were included as
the cases. Data from 679 volunteers were collected for controls from May to
December 1999. Among 1,302 of the study population 58 women had ever used HRT
(4.5%), which distributed to 3.2 per cent (20/623) in cases and 5.6 per cent
(38/679) in controls. From univariate analysis, age, age at menopause, number of
children, habitat, education, contraceptive pills, familial history of breast
cancer and HRT usage were associated with breast cancer (p-value<0.05). After
multivariate forward stepwise logistic regression analysis, there was no
association between HRT use and breast cancer (adjusted odds ratio (OR) = 0.61,
95% CI = 0.31-1.20). In subgroups analysis, women who had older age, higher
education level, history of taking contraceptive pills, or positive familial
history of breast cancer in second degree relatives had a decreased risk of
breast cancer, while those living outside Bangkok had an increased risk.
CONCLUSION: Hormonal replacement therapy in post-menopausal women was not
associated with increased risk of breast cancer.
6.) Safety
and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various
stages of the disease.
HIV Clin Trials 2002 Jan-Feb;3(1):21-6
Jirathitikal V, Bourinbaiar AS.
Immunitor Corporation, Chachoengsao, Thailand, and Salang Bunnag Foundation,
Bangkok, Thailand.
PURPOSE: To evaluate the safety and efficacy of an orally available, therapeutic
HIV vaccine (V-1 Immunitor) in patients who were not treated with antiviral
drugs. METHOD: All entrants who had been tested at least once at entry and at
postimmunization were considered for analysis. Main endpoints were vaccine
safety and differential effects on CD4 and CD8 cell counts, plasma HIV RNA
levels, and body weight change. Forty patients, 21 females (52%) and 19 males
(48%), aged 22-65 years (mean/median age, 35/32 years) with a mean 225/mm3 CD4
cells at baseline were retrospectively analyzed. Patients self-administered two
850-mg pills containing inactivated HIV-1 antigens b.i.d. for 27 weeks (median,
24 weeks). RESULTS: The treatment was well tolerated without significant adverse
effects. The mean body weight gain was 2.2 kg (p =.0004). The mean increase in
absolute CD4 and CD8 cells was 51 (18%; p =.0088) and 172 (16%; p =.0199)
cells/mm3. Viral load was measured by polymerase chain reaction (PCR) in 8
individuals; although overall decrease did not reach standard cut-off
statistical significance (Friedman p =.0588), the trend in reduction of viremia
attributable to vaccine administration was highly significant (Spearman
correlation test: r = 0.96, p =.0005). CONCLUSION: Mucosal delivery of HIV
antigens provides compelling results and deserves further evaluation in
placebo-controlled clinical trials.
7.) [Valvular
heart disease associated with benfluorex.] LIPASCOR-LIPAREX
Rev Esp Cardiol 2003 Feb;56(2):215-6
[Article in English, Spanish]
Rafel Ribera J, Casanas Munoz R, Anguera Ferrando N, Batalla Sahun N, Castro
Cels A, Pujadas Capmany R.
Servicios de Cardiologia. Hospital del Sagrado Corazon. Barcelona. Espana.
We report the first case of valvular heart disease due to benfluorex. A
50-year-old woman who had been taking the anorectic agent benfluorex
intermittently for one year developed severe fibrosis and regurgitation of the
mitral, aortic and tricuspid valves. Clinical, echocardiographic and
histopathological findings were analogous to those reported with fenfluramine
and dexfenfluramine. The similarity between the histopathological lesion
documented in patients treated with the appetite suppressants fenfluramine,
dexfenfluramine and benfluorex and the valvular lesions reported in valve
disease associated with ergot alkaloid use and carcinoid heart disease suggest a
common pathophysiological mechanism and a central role for serotonin in the
development of the disease.
8.)
Antidepressant-induced sexual dysfunction.
Ann Pharmacother 2002 Oct;36(10):1577-89
Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM.
The Lewin Group, Falls Church, VA 22042, USA.
OBJECTIVE: To review the evidence regarding antidepressant-induced sexual
dysfunction and address implications for treatment strategy and health plan
coverage policies for antidepressant medications. DATA SOURCES: Primary articles
were identified by a MEDLINE and HealthSTAR search to identify English-language
studies published between January 1986 and July 2000. Search terms included
sexual dysfunction or sexual function and antidepressants, fluoxetine,
sertraline, paroxetine, fluvoxamine, citalopram, venlafaxine, nefazodone,
bupropion, and mirtazapine. A cross-check of references cited in 10 published
reviews yielded additional in-scope articles. STUDY SELECTION AND DATA
EXTRACTION: Approximately 200 articles were identified, including 8 randomized
controlled trials and numerous open-label studies, case series, and case
reports. Of the randomized controlled trials, only 5 were designed to evaluate
the incidence of sexual dysfunction associated with antidepressant treatment.
Three additional randomized controlled trials included a structured assessment
of sexual dysfunction within an efficacy trial. Data extraction excluded case
reports, letters, and other limited study designs. A panel survey augmented
published reports. DATA SYNTHESIS: Sexual dysfunction is a relatively common
adverse effect of many of the antidepressants in common use today. Rates of
sexual dysfunction observed in clinical practice may be higher than those
reported in the product information for several agents. Selective
serotonin-reuptake inhibitors (SSRIs) appear to be the class of antidepressants
most likely to cause sexual dysfunction. Published studies suggest that between
30% and 60% of SSRI-treated patients may experience some form of
treatment-induced sexual dysfunction. Bupropion and nefazodone appear to be much
less likely to cause sexual dysfunction (<or=10% of patients). Mirtazapine also
appears to be associated with a low rate of sexual adverse effects. Panel
results largely reflect the consensus of the literature. CONCLUSIONS: Sexual
dysfunction is a common adverse effect of antidepressant treatment. Physicians
should monitor their patients for antidepressant-induced sexual adverse effects,
as these may affect compliance with therapy and ultimate treatment success. In
addition to the consequences for patient health and well-being, managed-care
organizations should be concerned with sexually related adverse effects of
antidepressants, insofar as additional healthcare resources may be required to
treat depressed patients in whom these adverse effects arise.
9.) [Chronic lupus erythematosus presenting as acneiform lesions]
Ann
Dermatol Venereol 2002 Jun-Jul;129(6-7):883-5
[Article in French]
Deruelle-Khazaal R, Segard M, Cottencin-Charriere AC, Carotte-Lefebvre I, Thomas
P.
Clinique dermatologique, Hopital Claude Huriez, CHRU, 59037 Lille Cedex, France.
[email protected]
BACKGROUND: Cutaneous manifestations of lupus erythematosus are numerous but
usually permit easy diagnosis. However, there are atypical lesions that can
mimic benign dermatologic disorders. We report on a patient with lesions of acne
leading to the diagnosis of chronic lupus erythematosus, and who subsequently
developed systemic lupus erythematosus. CASE REPORT: A 30-year-old woman
presented with inflammatory lesions and comedos on the face. The eruption
started after her last pregnancy and was refractory to local and general
treatment. She also complained of arthralgia, Raynaud's phenomenon and diffuse
alopecia. Cutaneous biopsy was characteristic of chronic lupus erythematosus.
Immunofluorescence microscopy of lesional skin showed a lupus band deposit.
Antinuclear antibodies were highly positive. The patient was successfully
treated with chloroquine. Three years later, the patient presented with
photodistributed eruption. Antinuclear antibodies were still positive and in
addition anticardiolipin antibodies were found. Final diagnosis was systemic
lupus erythematosus. DISCUSSION: Acneiform lesions are rarely reported in lupus
erythematosus. Only three similar cases were reported in literature. Atypical
and treatment-resistant eruptions should attract attention. Furthermore, the
occurrence of systemic lupus in chronic lupus erythematosus is not an unfrequent
phenomenon and the oestrogen-dependance of chronic lupus lesions may predict
this association.
10.) [Thrombotic
accidents induced by thalidomide: two cases]
Rev
Med Interne 2002 Aug;23(8):724-7
[Article in French]
Gachon J, Grob JJ, Richard MA.
Service de
dermatologie, hopital Sainte-Marguerite, CHU, 270, boulevard de
Sainte-Marguerite, 13274 Marseille, France.
INTRODUCTION: First used as a sedative, thalidomide was taken out the market
because of its teratogenicity. Despite other side effects, especially
neuropathies, this drug is now again prescribed in various autoimmune and
neoplasic diseases. Recently, venous or arterial thrombotic events have been
described after the introduction of thalidomide. EXEGESIS: In this report, we
describe two new venous thrombosis cases occurring during a treatment with
thalidomide. The first case is a 37-year-old man treated for a discoid lupus,
who developed three deep-vein thrombosis and a massive pulmonary embolism, with
recurrent thrombosis even with an efficient anticoagulation therapy until the
final stop of thalidomide. The second one is a 66-year-old woman treated with
thalidomide for a multiple myeloma and a melanoma in therapeutic escape, who
developed a deep-vein thrombosis two months after the beginning of her
treatment. Published reports suggest that most thrombotic events appeared under
three months after the introduction of the treatment and that thalidomide could
have acted as a precipitating or as a starting factor in a patient population
already at risk of thrombosis. Those complications should be particularly
severe, but the mechanism underlying thrombosis with thalidomide is unknown.
CONCLUSION: A complete coagulation check-up is advised before beginning a
treatment with thalidomide.
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DATA-MEDICOS/DERMAGIC-EXPRESS /FEBRUARY JOURNAL 2..003/ DR. JOSE
LAPENTA R.
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