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.      

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

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.     

Dieulafoy's duodenal ulcer. Report of two cases

Two cases of Dieulafoy's ulcer of the duodenum revealed by a severe digestive bleeding and histologically proved are reported. It is a rare localization of a rare disease which is particular by the presence of an abnormal vessel in the sub-mucosa layer of the digestive wall. Both patients were operated on and successfully treated by excision suture.     

Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery

AIM OF THE STUDY: To evaluate the results of laparoscopic splenectomy for hematologic diseases by a multicenter retrospective study. PATIENTS AND METHODS: Between 1991 and 1998, 275 patients (mean age: 40.4 years [18-93]) underwent splenectomy for idiopathic thrombocytopenic purpura (ITP) (n = 209, 76%), for hemolytic anemia (HA) (n = 37) including hereditary spherocytosis (n = 13) and auto-immune anemia (n = 24), lymphoma (n = 12), tumor (n = 6) and uncommon hematologic syndromes (n = 11). Laparoscopic splenectomy was attempted in every patient. The lateral approach was most commonly used with an anterior approach to the splenic hilar vessels, which were cut after hemostasis using a stapling gun; other techniques were also employed. RESULTS: The mean operating time was 165 minutes (45-360); it was shorter in the case of conversion (144 minutes) and became shorter with the operator's experience. Conversion was necessary in 55 patients (20%), due to hemorrhage in 2/3 of cases, related to splenic vessels (20 cases), short gastric vessels (9 cases), or injury of the spleen (8 cases). In ten cases (2%), conversion was necessary for extraction of the spleen. Conversion rate varied from 5.3 to 46.7%, depending on the surgical team. Univariate analysis of factors predisposing to conversion identified four causes: obesity; technique used to achieve hemostasis of the splenic hilar vessels; operator's experience; and presence of splenomegaly. An accessory spleen was found in 44 patients (16%). The weight of the spleen was more than 350 g in 43 patients (15.6%). There were no deaths. There were no significant complications in 236 patients (85.8%) and the mean hospital stay was 6.4 days. In comparison with patients who had a conversion, bowel function returned significantly earlier, use of analgesia was reduced and hospital stay was shorter. The overall morbidity rate was 13.8% (n = 38); morbidity rate was only 10.4% (n = 22) for laparoscopic splenectomy. In these 22 patients, the complications were: subphrenic collections (n = 5, 2.2%), abdominal wall infections (n = 5), thromboembolic events (n = 2), anemia (n = 2), pneumonia (n = 1), peptic ulcer (n = 1), bowel obstruction (n = 1), splenic vein thrombosis (n = 1). Re-operations were required in 4 patients (1.8%) because of hemorrhage, pancreatitis and bowel obstruction. Morbidity rate was significantly increased in the case of conversion (27%), obesity (20%), malignant disease (30%) and splenomegaly (21.8%). Forty-four patients (16%) received perioperative or postoperative blood transfusion and 23 (8.3%) received platelet transfusion. Mean time to return to normal activity was 21 days and was shorter in the absence of conversion (18.5 days versus 35 days). In patients with ITP, the mean platelet count was 240,000 after 3 months, and the failure rate was 8.3%. CONCLUSION: Laparoscopic splenectomy is a real alternative to conventional splenectomy for some hematologic diseases, particularly ITP and HA. The advantages are an uneventful postoperative course, a lower morbidity rate, a shorter hospital stay and an earlier return to normal activity. The limits of this technique are related to the operator's experience, the size of the spleen, the nature of the underlying disorders and patient characteristics, mainly obesity.