Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Acute ethanol counteracts the acquisition of aversive olfactory learning in infant rats.

Rodents are particularly prone to acquire associative memories during early stages of life. Yet, very little is known about how ethanol interacts with simultaneous associative learning acquired during postabsorptive periods. We have recently observed that preweanling rats avoid lemon odor previously paired with the intraoral infusion of a sapid sweet solution, a result likely to be caused by aversive consequences inherent to this procedure. Two experiments were conducted to analyze the effects of acute ethanol upon the acquisition of this avoidance response. Fourteen-day-old Wistar rats were intragastrically administered with ethanol (0.0, 0.25, 0.5, or 1.25 g/kg) and then exposed for 5 min to a lemon-scented chamber while being intraorally infused with sucrose (12% vol/vol). Four of such pairings were conducted immediately after ethanol administration. Control pups experienced these stimuli in an unrelated fashion. On postnatal day 15 animals were tested in a 5-min, two-way odor-preference test. Pups administered with vehicle during the acquisition phase exhibited a strong aversion to the lemon odor relative to control subjects. This avoidance response was reduced in pups that received 0.5 and 1.25 g/kg doses, whereas it completely vanished in those that received 0.25 g/kg dose. In a second experiment it was observed that, 10 min after the administration, blood ethanol concentrations attained with the 0.25, 0.5, and 1.25 g/kg doses were 11, 39, and 83 mg%, respectively. These data indicate that a very low dose of ethanol is able to counteract early aversive associative learning, a result likely to be mediated by anxiolytic properties of ethanol.     

Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

比较亮脯利特与醋酸甲孕酮注射剂皮下注射治疗子宫内膜异位症相关疼痛

目的：与亮脯利特比较，醋酸甲孕酮皮下注射（DMPA-SC104）治疗子宫内膜异位症的有效性和安全性。设计：3期多中心、随机、评价者盲法、对照比较试验。机构：加拿大和美国的临床试验点。患者：274例手术诊断的子宫内膜异位症妇女。干预：每3个月肌注DMPA-SC（104mg）或亮脯利特（11．25mg），共6个月。治疗后随访12个月。主要观察指标：5种子宫内膜异位症症状或体征的减轻（痛经、性交困难、盆腔痛、盆腔触痛、盆腔硬化）；骨密度（BMD）改变、低雌激素的症状、出血及体重的变化。结果：DMPA-SC104，在治疗末（6个月）减轻5种子宫内膜异位症症状或体征的4种，在12个月随访末（18个月）减轻全部5种症状，与亮脯利特统计学上效果相当。DMPA-SC104组患者显示在6个月较亮脯利特有更少的BMD损失，在随访的12个月又回到基线水平。     

BNP and ANP as diagnostic and predictive markers in heart failure with left ventricular systolic dysfunction.

BACKGROUND: The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers. AIMS: To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month. METHODS: Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) < or = 40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Students t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month. RESULTS: The mean EF in the patient sample was 33.43+/-6.52% and in the controls was 61.96 +/-3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78+/-54.36 and in the controls was 7.12+/-8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32+/-25.97 in patients and 11.18+/-7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found with both ARB or ACE-I treatment throughout the six months, with patients moving from classes III and IV to class II NYHA. Improvement of EF was also found, with transition of patients with lower EF (even <30%) to higher values. EF was higher in the ARB group at the sixth month. CONCLUSIONS: BNP and ANP can be useful diagnostic tools in hypertensive CHF patients with moderate-to-severe LV dysfunction. The decrease in BNP and ANP in the ARB group throughout six months, as well as the lower value at the sixth month, suggest a prognostic value of these parameters.