Time-kinetic study of repigmentation in vitiligo patients by tacrolimus or pimecrolimus

New topical immunomodulators have been reported to cause repigmentation of vitiligo lesions. However, time-kinetics of such repigmentation in different anatomic locations is not well known. We performed a randomized double-blind placebo control study with tacrolimus versus the vehicle and a nonrandomized control study with pimecrolimus to evaluate the time to reach significant pigmentation, its duration and extent in treated areas. Antioxidant status of serum was also assessed. Twenty patients, in the tacrolimus study, had one pair of lesions on different localizations, and 20 on face and/or upper limbs for pimecrolimus. The extent of repigmentation was evaluated by slides and mapmakings at baseline and every 4 weeks during 7 months. Adverse events were recorded. The derivatives of oxygen metabolites, the ferric reducing ability of serum and vitamin E were assessed. Three groups of patients were identified with the tacrolimus study. Eight had no significant change in response characterized by a parallel increase of repigmentation or none in treated and control areas. Nine had a better repigmentation to tacrolimus at fifth month of treatment. Three had a marked repigmentation in control areas at the end of treatment. Repigmentation was significant on the face compared to upper-limbs with pimecrolimus from fourth to seventh month. A significant reduction of oxidative stress and an increase in antioxidant capacity in serum of patients treated with topical tacrolimus was observed, while those treated with pimecrolimus did not show any significant changes but an increase in vitamin E. Our work defines three periods in repigmentation, triggering during the first 4 months, increase in pigmentation with tacrolimus and a plateau or a sustained repigmentation. The continuity of the treatment seems necessary to ensure a prolonged repigmenting effect and even an enhanced one, such as the one we observed on the face with pimecrolimus. The extent of repigmentation was more significant on the face compared to other locations probably due to differences in melanocyte density. Furthermore, we did not find any relationship between repigmentation and the duration of vitiligo. Tacrolimus was able to reduce the systemic oxidative stress independently from its repigmenting capacity. Both drugs were well tolerated.     

Ectopic thyroid gland in the porta hepatis and lingua.

A rare case of an ectopic thyroid gland in the porta hepatis and in the tongue in an asymptomatic euthyroid 24-year-old woman is reported. A solitary inhomogeneous, hypoechogenic and hyperechogenic mass in the porta hepatis was accidentally discovered by ultrasonography. Subsequent computed tomography demonstrated a heterogeneous, well-defined tumor with small calcifications without signs of environmental invasion. A hemangioma and focal nodular hyperplasia were excluded by blood pool and hepatobiliary scintigraphy. Surprisingly, fine-needle aspiration cytology revealed normal thyroid tissue. (123)I-scintigraphy confirmed the presence of ectopic dual thyroid tissue in the hepatic porta and lingua. At clinical inspection the lingual thyroid gland was palpable and visible, and appeared solid and spheroidal. The subhepatic, ectopic thyroid mass was resected. Postoperatively, thyroid hormone replacement was started to prevent an enlargement of the lingual thyroid. Today, 4 years after surgery, the patient remains euthyroid.     

Serum IL-2 and platelet-associated immunoglobulins are good prognostic markers in immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.     

Circadian Rhythms of Heart Rate Variability in Hypertrophic Cardiomyopathy

Background: It has been hypothesized that an interaction between sympathetic nervous activity and an abnormal myocardium plays a role in the development and progression of hypertrophic cardiomyopathy (HCM). Methods: In the present study we investigated cardiac autonomic function by 24-hour spectral analysis of heart rate variability (HRV) in 18 patients with HCM, without evidence of heart failure, and 18 controls of similar age. Results: We found a significant reduction of 24 hour variance in HCM patients relative to controls (15,000 ± 9480 ms² vs 24,720 ± 12,450 ms² respectively; p < 0.05). Moreover, a loss of the expected day-night changes in the low frequency (LF) spectral component (expressed in normalized units), and LF/HF ratio (HF; high frequency component) were observed in HCM patients. Decreased day-night changes in LF/HF ratio were previously reported in patients with mild hypertension, uncomplicated coronary disease, and after myocardial infarction, conditions in which it seems to exist a higher than normal sympathetic activity. No significant correlations were found between HRV indices and echocardiographic standard measures of systolic and diastolic function parameters. Conclusions: These data are consistent with the presence of an alteration in neural modulation of heart period in HCM patients, noninvasively detectable by continuous 24 hour HRV analysis.     

Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses.

BACKGROUND: Cardiac resynchronization therapy (CRT) for congestive heart failure patients with delayed left ventricular (LV) conduction is clinically beneficial in approximately 70% of patients. Unresolved issues include patient selection, lead placement, and efficacy of LV pacing alone. Being an electrical approach, detailed electrical information during CRT is critical to resolving these issues. However, electrical data from patients have been limited because of the requirement for invasive mapping. OBJECTIVES: The purpose of this study was to provide observations and insights on the variable electrophysiologic responses of the heart to CRT using electrocardiographic imaging (ECGI). METHODS: ECGI is a novel modality for noninvasive epicardial mapping. ECGI was conducted in eight patients undergoing CRT during native rhythm and various pacing modes. RESULTS: In native rhythm (six patients), ventricular activation was heterogeneous, with latest activation in the lateral LV base in three patients and in the anterolateral, midlateral, or inferior LV in the remainder of patients. Anterior LV was susceptible to block and slow conduction. Right ventricular pacing improved electrical synchrony in two of six patients. LV pacing in three of four patients involved fusion with intrinsic excitation resulting in electrical resynchronization similar to biventricular pacing. Although generally electrical synchrony improved significantly with biventricular pacing, it was not always accompanied by clinical benefit. CONCLUSION: Results suggest that (1) when accompanied by fusion, LV pacing alone can be as effective as biventricular pacing for electrical resynchronization; (2) right ventricular pacing is not effective for resynchronization; and (3) efficacy of CRT depends strongly on the patient-specific electrophysiologic substrate.     

Outcomes following cardiopulmonary resuscitation in an emergency department of a low- and middle-income country

Background

Cardiopulmonary resuscitation (CPR) is a key component of emergency care following cardiac arrest. A better understanding of factors that influence CPR outcomes and their prognostic implications would help guide care. A retrospective analysis of 800 adult patients that sustained an in- or out-of-hospital cardiac arrest and underwent CPR in the emergency department of a tertiary care facility in Karachi, Pakistan, between 2008 and 15 was conducted.

Methods

Patient demographics, clinical history, and CPR characteristics data were collected. Logistic regression model was applied to assess predictors of return of spontaneous circulation and survival to discharge. Analysis was conducted using SPSS v.21.0.

Results

Four hundred sixty-eight patients met the study’s inclusion criteria, and overall return of spontaneous circulation and survival to discharge were achieved in 128 (27.4%) and 35 (7.5%) patients respectively. Mean age of patients sustaining return of spontaneous circulation was 52 years and that of survival to discharge was 49 years. The independent predictors of return of spontaneous circulation included age ≤?49 years, witnessed arrest, ≤?30 min interval between collapse-to-start, and 1–4 shocks given during CPR (aOR (95% CI) 2.2 (1.3–3.6), 1.9 (1.0–3.7), 14.6 (4.9–43.4), and 3.0 (1.4–6.4) respectively), whereas, age ≤?52 years, bystander resuscitation, and initial rhythm documented (pulseless electrical activity and ventricular fibrillation) were independent predictors of survival to discharge (aOR (95% CI) 2.5 (0.9–6.5), 1.4 (0.5–3.8), 5.3 (1.5–18.4), and 3.1 (1.0–10.2) respectively).

Conclusion

Our study notes that while the majority of arrests occur out of the hospital, only a small proportion of those arrests receive on-site CPR, which is a key contributor to unfavorable outcomes in this group. It is recommended that effective pre-hospital emergency care systems be established in developing countries which could potentially improve post-arrest outcomes. Younger patients, CPR initiation soon after arrest, presenting rhythm of pulseless ventricular tachycardia and ventricular fibrillation, and those requiring up to four shocks to revive are more likely to achieve favorable outcomes.

     

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

Rapid molecular characterization of mutations leading to unstable hemoglobin β-chain variants

Summary Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable -chain variants, which produce a -thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the -globin gene. We describe the use of the DGGE method for rapid characterization of -chain variants and report a new missense mutation in the -globin gene third exon, 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin.