Preventing melasma recurrence: prescribing a maintenance regimen with an effective triple combination cream based on long-standing clinical severity.

BACKGROUND: The relapsing nature of melasma emphasizes the need to maintain efficacy achieved after acute treatment. OBJECTIVE: To compare clinical efficacy and safety of two 6-month Triple Combination (TC; containing fluocinolone acetonide, hydroquinone and tretinoin) maintenance regimens in subjects with moderate to severe melasma, after daily treatment up to 8 weeks. METHODS: This randomized, investigator-blinded, controlled study had a maintenance phase of 6 months. Sixteen centres in Brazil and Mexico enrolled 242 subjects 18 years or older attaining no or mild melasma after 8 weeks of daily TC applications. Subjects were randomized to receive TC in a twice weekly or tapering regimen [3/week (1st month), 2/week (2nd month), 1/week (4th month)]. Efficacy and safety measurements included median time to relapse and relapse-free rate, Global Severity Score, Melasma Area and Severity Index score (MASI), subject's assessment, quality of life questionnaire (MelasQol), and adverse events. RESULTS: The majority (78.8%) had no or mild melasma (GSS ≤ 1) at week 8 and entered maintenance phase. After 6 months, 53% of patients remained relapse-free with improved quality of life, and time to relapse was similar between groups (about 190 days). Melasma severity at study entry, not maintenance baseline, influenced relapse rate. The twice weekly regimen tended to show better effectiveness in postponing relapse in severe melasma. Both regimens were safe. CONCLUSIONS: After resolution of melasma with TC, maintenance therapy over 6 months was successful in preventing relapse in over half of the patients who entered maintenance phase. Prescribing medicines should be adapted to patients based on melasma severity.

T cell homeostasis: thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors.

We developed a novel experimental strategy to study T cell regeneration after bone marrow transplantation. We assessed the fraction of competent precursors required to repopulate the thymus and quantified the relationship between the size of the different T cell compartments during T cell maturation in the thymus. The contribution of the thymus to the establishment and maintenance of the peripheral T cell pools was also quantified. We found that the degree of thymus restoration is determined by the availability of competent precursors and that the number of double-positive thymus cells is not under homeostatic control. In contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely independent of the number of precursors and of the number of thymus cells. Peripheral "homeostatic" proliferation and increased export and/or survival of recent thymus emigrants compensate for reduced T cell production in the thymus. In spite of these reparatory processes, mice with a reduced number of mature T cells in the thymus have an increased probability of peripheral T cell deficiency, mainly in the naive compartment.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats.

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Prediction of enthalpy and standard Gibbs energy of vaporization of haloaromatics from atomic properties.

Halogenated benzenes form a class of pollutants with a huge number of members - 1504 distinct benzene compounds, where one or more hydrogen atoms are replaced by halogens, may exist theoretically. This study presents a user friendly method for accurate prediction of vapor pressures and enthalpies of vaporization, at 298.15 K, of any mono or poly halobenzene compound. The derived equations for the prediction of those vaporization properties depend just on the number of each constituent halogen atom. This is a consequence of the absence of intramolecular interactions between the halogen atoms, revealed after examining vaporization results of ca. 40 halogenated benzenes. In order to rationalize the estimation equations, the contribution of the halogen atoms for the referred to above properties of vaporization was decomposed into two atomic properties - the volume and electron affinity. Extension of the applicability of the estimation method to substituted benzenes containing other substituent groups beyond halogen atoms as well as to some polycyclic aromatic species was tested with success.

Serum levels of bothropic venom in patients without antivenom intervention.

Serum kinetics of bothropic venom were evaluated in eight snakebite patients, who due to a national shortage, received no specific antivenom therapy. The cases were clinically classified as mild, moderate, and severe. Patients were bled sequentially and serum levels of venom were assayed by ELISA. Venom level ranges differed among the groups, with peak levels of less than 13 ng/ml, 32 ng/ml, and 120 ng/ml for the mild, moderate, and severe groups, respectively. There was no clear pattern of kinetics in the groups. Regression analysis involving the variables severity and peak venom levels yielded a statistically significant correlation (rs = 0.80, P less than 0.05). These data indicate that different amounts of circulating venom correlate with clinical severity, even in highly complex venoms, and stress the importance of careful clinical classification in the proper management of bothropic incidents.

Enzyme-linked immunosorbent assay for the detection of Bothrops jararaca venom.

This study reports an enzyme-linked immunosorbent assay for detecting Bothrops jararaca venom in fluids, employing the sandwich method with biotin/avidin amplification. The assay exhibits high accuracy in correlating optical densities with venom concentrations (r = 0.98), high reproducibility, low background and limited cross-reactivity with venom from other snake genera. Nevertheless, it was unable to distinguish among venoms from different bothropic species. Using this method we evaluated the serum kinetics of Bothrops jararaca venom in C57BL/6 mice. High concentrations were found in serum just 15 min after injection (151 +/- 41 ng/ml; mean +/- S.D.), followed by a progressive fall (102 +/- 46, 74 +/- 39 and 50 +/- 22 ng/ml after 1, 3 and 6 hr respectively), being undetectable by 24 hr. Such serum kinetics indicates a pattern of a rapid absorption of venom from the inoculation site, followed by a slow and progressive drop in its serum levels. This ELISA was a reliable tool in the determination of Bothrops jararaca venom levels in mouse serum, and may become useful in other fields of bothropic venom research.

Effect of 5-Fluorouracil on corneoscleral wound healing.

5-Fluorouracil has been advocated as an adjunct to filtration in combined extracapsular cataract extraction, intraocular lens implantation, and trabeculectomy; however, it may exert an undesirable inhibitory effect on cataract wound healing. Accordingly, the effect of 5-fluorouracil on corneoscleral wound healing was evaluated in an animal model. During the first 2 weeks following creation of full-thickness corneoscleral wounds, 40 rabbits were randomly assigned to receive either 10 subconjunctival injections of 5 mg 5-fluorouracil or normal saline. After sacrifice, 2, 4, 8, or 16 weeks postoperatively, the tensile strength of a 5-mm wound segment from each rabbit was measured with a tensiometer; histologic analysis was performed on untested portions of the wounds. 5-Fluorouracil was found to produce a trend toward decreased wound strength; however, this effect diminished over time. Histologic analysis was consistent with early inhibition of healing with resumption of healing following discontinuation of the drug. We conclude that 5-fluorouracil delays healing and development of tensile strength in rabbit corneoscleral wounds.

Immunological studies with the venom of the scorpion Tityus serrulatus.

1. We describe a "sandwich" enzyme-linked immunosorbent assay (ELISA) sensitive to quantities of scorpion (Tityus serrulatus) venom (TsV) in the range of 1-3 ng/ml sample. 2. Cross-reactivity with the venom from the rattlesnake Crotalus durissus terrificus and with venoms from several snakes of the Bothrops genus was detected only at concentrations higher than 1 microgram/ml sample. 3. A conventional ELISA is also described for the detection of antibodies against TsV. 4. Analysis by Western Blot (WB) demonstrated a 25-kDa protein band common to TsV and to the venoms of Bothrops moojeni, B. jararacussu and B. jararaca. 5. Venom from C. d. terrificus exhibited WB cross-reactive bands of 16 and 25 kDa with TsV.

[Significance of the persistence of ST segment elevation in anterior infarction]. / Significado da persistência da elevação do segmento ST no enfarte anterior.

OBJECTIVE: Persistent ST segmentary elevation in anterior myocardial infarction was classically attributed to ventricular aneurysm. This association is now considered controversial. We studied the association between this electrocardiographic finding and the left ventricular wall motion abnormalities and global function. DESIGN: Retrospective study. SETTING: Patients admitted to Hospital de Pulido Valente Coronary Care Unit in Lisbon with anterior myocardial infarction who were submitted to angiographic study. PATIENTS: 94 patients were included in the study. METHODS: The global ejection fraction, the regional wall motion abnormalities, the coronary artery disease extension, the patency and the proximal involvement of the left anterior descending artery were investigated. RESULTS: 56 of the 94 patients (60%) had persistent ST segment elevation and 38 (40%) had isoelectric ST segment. The ejection fraction was markedly depressed in the group with elevated ST segment (36.2 SD 17.6) in contrast with the group with isoelectric ST segment (49.3 SD 14.8) (p < 0.001). The group with persistent ST segment elevation had more advanced degrees of left ventricular asynergy (42/58-75%) than the group with isoelectric ST segment (12/38-32%) (p = 0.02). The other studied angiographic variables did not differ between the two groups. CONCLUSIONS: The group with persistent ST segment elevation was associated with advanced degrees of left ventricular asynergy and greater left ventricular function depression. The ventricular aneurysm was exclusive of the first group.

[Stress tests in old age. The choice of the stress protocol]. / Provas de esforço na terceira idade. Escolha do protocolo de esforço.

OBJECTIVE: To evaluate, in an elderly Portuguese population, the diagnostic capacities of the most popular treadmill stress test protocols. DESIGN: Retrospective study of an elderly Portuguese population submitted to a stress test. PATIENTS AND METHODS: A population of 45 patients (35 male), aged 65 or more years, consecutively submitted to a stress test. The average age of the group was 67.8 +/- 2.9 years. The three protocols (Bruce, Bruce Modified and Naughton) were comparatively studied in terms of the patients capacity to execute the protocol, capacity to obtain a maximum and a diagnostic stress test, and the complications of the stress test protocol. MAIN RESULTS: The Bruce protocol was used in 19 patients, the Bruce Modified in 13 patients and the Naughton protocol in 13 patients. The three protocols did not lead to any complication. The Bruce protocol led to a larger increment in heart rate (p < 0.001) and to larger maximum rate pressure product (p < 0.05) than the Naughton one. The Bruce protocol obtained a larger number of diagnostic tests (p < 0.01) and a significantly lower number of inconclusive stress tests. The Naughton protocol led to a larger duration of the exercise tests and was not suitable for some of the elderly patients owing to the exhaustion of the protocol. The results obtained with the Bruce Modified protocol were among those of other two protocols. CONCLUSIONS: In the elderly, the stress tests are safe and useful in the diagnosis of exercise induced ischemia and in the stratification of cardiovascular risk. From the protocols studied, the Bruce protocol was the most adequate, globally speaking, for this group of patients. The Bruce protocol presented a better diagnostic capacity with no complications related to the protocol.

Validation of a melasma quality of life questionnaire for Brazilian Portuguese language: the MelasQoL-BP study and improvement of QoL of melasma patients after triple combination therapy.

BACKGROUND: Pigmentation disorders, such as melasma, greatly influence the quality of life (QoL) of affected individuals who usually consider the disorder to be more severe than the objective clinical scores. Several instruments have been successfully developed to evaluate QoL. However, they must be adapted to the target population in terms of language and cultural diversity. The first, specific QoL questionnaire for melasma (MelasQoL) was developed for English speaking patients. OBJECTIVES: To validate the Brazilian Portuguese version of the MelasQoL evaluation questionnaire for patients with melasma (MelasQoL-BP) and to assess the impact of treatment with a triple combination cream (hydroquinone, fluocinolone acetonide and tretinoin) on the QoL of patients with moderate-to-severe melasma. METHODS AND RESULTS: Three hundred individuals from the five Brazilian geographic regions took part in this multicentre study. Their mean age was 42 years and skin phototype distribution was: type II 7.0% of patients, III 23.7%, IV 42.7% and V 22.7%. Melasma Area and Severity Index (MASI), MelasQoL-BP and the short version of the QoL assessment instrument from the World Health Organization (WHOQOL-BREF) were used to assess melasma severity and QoL at baseline. MelasQoL-BP was previously translated and culturally adapted from the English version, with participation of the authors and according to the standards of the World Health Organization (WHO). From the original sample, we randomized150 volunteers to treat melasma and repeated the evaluation after 8 weeks. The analysis of the MelasQoL-BP baseline answers demonstrated an important impact of the disease on skin appearance (65% of patients were bothered all the time or most of the time), frustration (55%), embarrassment (57%) and influence of the disease on interpersonal relationships (42%). Forty-three per cent of patients felt not attractive or even dirty due to their skin condition. MelasQoL-BP results showed significant internal consistency (Cronbach's alpha coefficient 0.919; P < 0.001) and good correlation with MASI scores. After treatment, the global assessment showed good or excellent results in 91.4% of the patients. The clinical outcome was not associated with the initial MASI score (P = 0.814; chi-square), skin colour (P = 0.449; probability ratio) or skin pigmentation (P = 0.814; chi-square). There was also a significant reduction on MelasQoL-BP scores (Wilcoxon test; P < 0.001) after treatment, with the mean +/- SD results shifting from 44.4 +/- 14.9 at baseline to 24.3 +/- 15.5 after treatment. The analysis of the MelasQoL-BP before and after treatment showed an important effect of the impact of treatment on a number of QoL measures. Of note, skin appearance (69.8 vs. 10.1% of patients were bothered all the time or most of the time, respectively), frustration (59.7% vs. 12.2%, respectively), embarrassment (56% vs. 9.3%, respectively) and influence of the disease on interpersonal relationships (35.3% vs. 5.8%, respectively) were greatly improved. CONCLUSIONS: This study demonstrates that MelasQoL-BP is a valid instrument and can be used to evaluate the quality of life and response to melasma treatment in Brazilian patients. The triple combination treatment produced significant results, regarding both clinical severity and quality of life.

Plague in Brazil during two years of bacteriological and serological surveillance.

In north-east Brazil, where plague infection is endemic, bacteriological and serological methods were employed during a two-year period to determine accurately the occurrence of human infection and to define certain epidemiological features of both human and rodent infection. There were 67 confirmed cases of plague, predominantly among males and children. Most of these cases occurred in two inland rural plateaux of Ceara State. Clustering of cases in place and time was common, as was a history of contact with rats. Peak occurrence was in November 1978, during the warm, harvest time of year. Rodent surveillance resulted in isolation of Yersinia pestis from 33 animals, most of them from the field rodent, Zygodontomys pixuna, in the States of Pernambuco and Ceara. Our results indicate a decline in the number of human cases from previous years but show that several foci remain active and that serological testing, in addition to routine bacteriological testing, can assist workers in maintaining the surveillance of both human and rodent plague in Brazil.

Nail abrasion.

Certain diseases of the nail complex cause hyperkeratosis or alterations of the shape of the nail plate. These conditions may be painful, may decrease the penetration of topical medicaments and may be ugly. The nail plate abrasion, performed with dermabrader device or sandpaper, has application in patients suffering from onychomycosis, psoriasis, subnail infections and haematomas. The technique facilitates the collection of scales for mycological examination, decreases treatment time (of topical monotherapy) for onychomycosis and provides greater comfort for the patient by reducing nail plate thickness. It can also be useful for the partial removal of the nail plate in cases of haematomas and subnail infections. Nail abrasion is an effective and inexpensive method, easily applied in either nail pathologies with hyperkeratosis of the nail plate or in those requiring partial removal of the plate.

Improving botulinum toxin therapy for palmar hyperhidrosis: wrist block and technical considerations.

Botulinum A exotoxin has become an excellent therapeutic option to treat focal hyperhidrosis, but when the problem affects the palmar region the technique has some drawbacks. Pain with injection is difficult to tolerate and the large dose needed to treat both hands are two concerns, as well as muscle weakness secondary to botulinum toxin diffusion and the possibility of antibody production. All these problems limit the number of patients treated. The author's suggestion is to treat only the dominant hand, after performing a wrist block. The use of a device adapted from a cartridge rubber may help to control the injection depth and the risk of muscular weakness.

Renal dysfunction in Brazilian lead workers.

In this study, renal function of 52 workers of a primary lead smelter located in Northeast Brazil was compared to a reference group of 44 otherwise similar workers of a paper mill. Renal dysfunction, defined by a serum creatinine level greater than or equal to 1.5 mg/dl, was found in 17 (32.7%) workers at the lead smelter, the exposed group, but in only 1 (2.3%) individual from the reference group. Workers from the exposed group also showed significantly higher mean serum uric acid levels. Renal dysfunction of workers from the exposed group was statistically associated with duration of the employment at the smelter and with age, but not with the levels of lead and zinc protoporphyrin in blood and delta-aminolevulinic acid in urine. The two groups presented similar rates of arterial hypertension. However, arterial hypertension was much more strongly associated with renal dysfunction in the lead workers.