Cicatricial (Scarring) Alopecias

Cicatricial (scarring) alopecia forms a group of disorders in which the common final pathway is the destruction of the hair follicle unit that is replaced by fibrous tissue. Hair loss may occur as a primary event when the follicle is the main target of the disease process (primary cicatricial alopecias) or as a secondary event when the follicle act as an 'innocent bystander' in the course of a disease occurring outside of the follicular unit (secondary cicatricial alopecias). Permanent hair loss may also occur in the late phases of some nonscarring alopecias that are called 'biphasic alopecias.' Primary cicatricial alopecia accounts for 5% of all trichologic consultations at the Section of Dermatology, University of Genoa, Genoa, Italy. Considering that hair loss has a strong impact on patients' psychology and quality of life, and that cicatricial alopecias can be associated with underlying systemic implications, it is extremely important that every clinician is familiar with the diagnosis and treatment of the different types of cicatricial alopecia. An accurate clinical assessment integrated with (video) dermatoscopy and histopathologic studies permits a high standard performance of correct diagnoses. A brief review of our current knowledge of disease pathogenesis and the hypothetical disease mechanisms is presented. Some practical considerations for improving the 2001 North American Hair Research Society working classification of the primary cicatricial alopecias are suggested. The aim of treatment is to slow or stop the progression of the inflammatory waves and the scarring process at the earliest phase of involvement. Recommendations for therapy are based upon a literature review, personal experience, expected adverse effects, and some pragmatic considerations such as the cost and patient compliance.     

Quantification of Tumor Microvascularity with Respiratory Gated Contrast Enhanced Ultrasound for Monitoring Therapy

The aim of this feasibility study was to evaluate the response to cytotoxic and antiangiogenic treatment of colorectal liver metastasis using respiratory gated contrast enhanced ultrasonography. Seven patients were monitored with contrast enhanced ultrasound. Sulfur hexafluoride filled microbubbles (SonoVue; Bracco S.P.A., Milan, Italy) were used as contrast agent and the scans were performed with a nonlinear imaging technique (power modulation) at low transmit power (MI=0.06). The mean image intensity in the metastatic lesion and in the normal liver parenchyma were measured as a function of time and time-intensity curves from linearized image data were formed. A novel respiratory gating technique was utilized to minimize the effects of respiratory motion on the images. A reference position of the diaphragm (or other echogenic interface) was selected and all frames where the diaphragm deviated from that position were rejected. The wash-in time (start of enhancement to peak) of metastasis and adjacent normal liver parenchyma was measured from time-intensity curves. The ratio of wash-in time of the lesion to that of the normal parenchyma (WITR) was used to compare the perfusion rate. In a reproducibility study (five patients), the average deviation of WITR was found to be 9%. There was an increase in the WITR for patients responding to treatment (mean WITR increase of 17% after first dose of treatment and 75% at the end of the therapy). In four out of five patients (80%) responding to therapy WITR predicted their response from the first treatment. All six patients that responded to therapy by the end of the therapy cycle (6–9 doses) were correctly predicted by using WITR. The WITR may be a new surrogate marker indicative of early tumor response for colorectal cancer patients undergoing cytotoxic and antiangiogenic therapy. (E-mail: maverk@ucy.ac.cy)     

The impact of psychological functioning upon systemic sclerosis patients' quality of life

OBJECTIVE: To access health-related quality of life (HRQOL) in systemic sclerosis (SSc) patients using the World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF), and to identify the association between clinical, psychopathological, and personality parameters and SSc patients' HRQOL. METHODS: Fifty-six patients with SSc were compared with 72 patients with rheumatoid arthritis (RA), 43 with systemic lupus erythematosus (SLE), 34 with Sj?gren syndrome (SS), and 74 healthy controls. A wide range of clinical information was collected and the following self-report instruments were used: the WHOQOL-BREF, the General Health Questionnaire, the Symptom Distress Check List, the Hostility and Direction of Hostility Questionnaire, the Defense Style Questionnaire, and the Sense of Coherence scale. RESULTS: HRQOL perceived by SSc patients was significantly impaired compared with healthy controls. Initial examination of HRQOL across groups of rheumatology patients revealed similar HRQOL, but when age, pain, psychopathology, and coping strategies were taken into account, SSc patients had impaired physical health QOL in comparison with RA, SLE, and SS patients. Arthritis-related pain was closely associated with SSc patients' HRQOL. Elevated psychological distress symptoms as well as certain personality traits, such as maladaptive defenses and lower sense of coherence, were also associated with diminished HRQOL. CONCLUSIONS: Impaired psychological functioning is associated with diminished HRQOL in SSc, and consequently, treatment of depressive symptoms should be considered a priority. Moreover, assessment of HRQOL should only be used in conjunction with specific psychological distress measurements, to detect the influence of psychopathology on HRQOL.     

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease.     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.     

Nuttall technique: A method for subumbilical incisional hernia repair revised

Background Large ventral incisional hernias are frequently repaired either by open or by laparoscopic mesh technique. The technique recommended by Nuttall has been used for the repair of large subumbilical incisional hernias but has not been popularized. Materials and methods From 1991 to 2005, 21 patients, mean age 64.6 ± 13 (44–86) years, underwent repair of large subumbilical incisional hernia with the Nuttall technique by which the rectus muscles are detached from the symphysis pubis and transposed to the opposite side. The exerted tension is minimal to the underlying tissues, and no prosthetic material is required to reinforce the abdominal wall. Results Morbidity was recorded in five patients (23.8%). The median follow-up time was 84 months, and the recurrence rate was 4.8% (one patient). Conclusions Although a small number of patients have undergone repair with the Nuttall technique, the long-term results of the method seem to be encouraging for the repair of large subumbulical incisional hernias.     

A new HPLC method to determine Donepezil hydrochloride in tablets.

A HPLC stability-indicating assay for Donepezil hydrochloride in tablets was developed and validated. Donepezil hydrochloride is a reversible inhibitor of acetylcholinesterase, indicated for the treatment of mild to moderate dementia of the Alzheimer's type. The HPLC method was performed with a reversed phase C18 column, detection at 268 nm and a mixture of methanol, phosphate buffer 0.02 M and triethylamine (50:50:0.5) as mobile phase. Typical retention time for Donepezil was 9 min. The method was statistically validated for linearity, accuracy, precision and selectivity following ICH recommendations. Due to its simplicity and accuracy, the method can be used for routine quality control analysis.     

The cost of treating children and adolescents with injuries to their permanent incisors at a dental hospital in the United Kingdom

Abstract –  The aim was to estimate the total cost, including the direct costs (outpatient costs) and indirect costs (missed working day) of treating children and adolescents with traumatic injuries to their incisors. Factors such as the number of treatment visits and the success of outcome were also investigated. The sample was taken from patients who attended the dental trauma clinic at a London teaching hospital between 1990 and 2001. Eighty-one patients, with 111 traumatized incisors were included in this study. The mean age was 9.9 (SD = 2.33) years and the male:female ratio was 3:2. The median number of visits and median treatment duration were eight visits and 21 months, respectively. Sixty-two per cent of the patients lived >5 miles and 25% lived >10 miles from the hospital; 44% of the patients had uncomplicated and 56% had complicated trauma to their incisors. Accidental falls, falls involving a second person, sport-related injuries and road accidents accounted for 30, 22, 22 and 17% of the total injuries. For uncomplicated trauma, 97% of the patients had a successful outcome but this was reduced to 58% for complicated trauma. The average total cost of treating a patient with one traumatic injury was £856. The best predictor for higher number of visits and unsuccessful outcome was complicated trauma with odd ratios of 4.5 and 24 (95% CI 1.5–13.7 and 2.9–194.2), respectively. It was concluded that the indirect cost was a considerably large proportion (39%) of the total cost. More specialists in paediatric dentistry are needed to improve access to care locally and thus reducing the indirect travelling cost.