Biomedical subjects
Publications and source records attributed to Joaquim Ferreira.
The authors analyse the correspondence between Eça de Queiroz, a well-known Portuguese writer, and his wife, in 1900, describing the neurological disease of their second son, José Maria d'Eça de Queiroz, know as Zezé. In those letters, the writer mentions chorea as his son diagnosis, explaining in detail its clinical picture. In addition, the writer reveals the medical thoughts of the time about the aetiology, treatment and natural history of Sydenham's Chorea.
Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD). The full-length open reading frame and splice sites of the LRRK2 gene (51 exons) were studied by genomic sequencing in 60 probands with ADPD (83% Italian). Pathogenic mutations were identified in six probands (10%): the heterozygous p.G2019S mutation in four (6.6%), and the heterozygous p.R1441C mutation in two (3.4%) probands. A further proband carried the heterozygous p.I1371 V mutation, for which a pathogenic role could not be established with certainty. In total, 13 novel disease-unrelated variants and three intronic changes of uncertain significance were also characterized. The phenotype associated with LRRK2 pathogenic mutations is the one of typical PD, but with a broad range of onset ages (mean 55.2, range 38-68 years) and, in some cases, slow disease progression. On the basis of the comprehensive study in a large sample, we conclude that pathogenic LRRK2 mutations are frequent in ADPD, and they cluster in the C-terminal half of the encoded protein. These data have implications both for understanding the molecular mechanisms of PD, and for directing the genetic screening in clinical practice.
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It is well stated in the literature that medical treatment for peptic ulcer is based on a combination of proton pump inhibitors (PPIs) and antibiotics to eradicate Helicobacter pylori. This treatment is associated with a high rate of immediate success and a low rate of recurrence at 12 months, although it is not effective in all patients. Peptic ulcer (PU) perforation is a serious problem that leads to high complication and mortality rates. Surgical treatment, with its various possibilities, constitutes the ideal treatment. Surgical intervention in these cases, however, can be directed to treating the perforation alone, or it can offer definitive treatment of the ulcer itself. With the hope of establishing why such complications and mortality were seen in the patients in our hospital population, we gathered the facts about PU perforations and the types of surgery performed. We studied 210 consecutive patients (150 men, 60 women) who had undergone surgery at our hospital because of perforation between January 1, 1990 and December 31, 2000. The patients' median age was 53.0 +/- 20.6 years (men 47.7 +/- 17.3 years; women 66.3 +/- 22.0 years). Altogether, 86 patients had significant associated illnesses, 62 were admitted more than 24 hours after the perforation, and 25 were admitted in shock. We performed resections in 10 patients; 88 patients were treated by suturing the perforation with or without a patch of epiploon; and 112 underwent a troncular vagotomy with drainage (VT + Dr). A total of 21 patients died (10%). Significant risk factors that led to complications were identified by statistical studies. They were a perforation that had been present more than 24 hours, the coexistence of significant associated illnesses, and resection surgery. The significant risk factors that led to death were the presence of shock at admission, the coexistence of significant illnesses, and resection surgery. There was no statistically significant difference concerning morbidity and mortality between simple closure of the perforation and definitive surgery (VT + Dr).
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Gastric cancer is a disease in which the main treatment is surgical extirpation. The modifications introduced in the surgical treatment over the last decades were accompanied by a clear increase of survival, which reaches global values of 61% at 5 years in Japan. One of the reasons that contribute to this improvement is early diagnosis of the lesions. In the period between January 1, 1990 and December 31, 1999 662 patients with gastric adenocarcinoma were treated in the Service of Surgery 1 of our hospital; 110 were refused surgical treatment. Of the resected patients, 91 (21.4%) were classified as early gastric cancer according to the definition of the Japanese Society of Digestive Endoscopy. There were 30 women and 61 men, with a median age of 60.2 +/- 15 years; 3 patients had a preoperative diagnosis of gastric ulcer; 2 others were operated without recent histology; and 1 patient was urgently resected for a bleeding ulcer. In all the remaining patients biopsy confirmed the presence of cancer (89%) or serious dysplasia (4.6%). The lesions had been distributed essentially in the medium 1/3 (48.3%) and distal 1/3 of the stomach. Subtotal gastrectomy was accomplished in 48 patients, total gastrectomy in 40, total desgastrogastrectomy in 3, and in 9 patients the surgery involved the spleen (8 patients) and the spleen and tail of the pancreas in 1 patient. Lymphadenectomy was not performed in 5 patients, lymph nodes by the first lymph node barrier were removed in 25 patients and by the second barrier in 61 patients (67%). Median tumor size was 26 +/- 1.8 mm. The lesion reached the mucosa in 46 patients and the mucosa and submucosa in 45. In 6 patients the removed lymph nodes were microscopically invaded (6.7%). Five patients died (5.7%). The median follow-up of the patients is 41 +/- 26 months; 7 patients died (8.1%) during this period; 4 died unequivocally of disease progression. The median survival of patients was 85% at 5 years and 80% at 10 years. In our series, survival was affected by the presence of invaded lymph nodes, not by the penetration in depth of the lesion or the size of the tumor.
Mutations in the LRRK2 gene have been identified in families with autosomal dominant parkinsonism. We amplified and sequenced the coding region of LRRK2 from genomic DNA by PCR, and identified a heterozygous mutation (Gly2019 ser) present in four of 61 (6.6%) unrelated families with Parkinson's disease and autosomal dominant inheritance. The families originated from Italy, Portugal, and Brazil, indicating the presence of the mutation in different populations. The associated phenotype was broad, including early and late disease onset. These findings confirm the association of LRRK2 with neurodegeneration, and identify a common mutation associated with dominantly inherited Parkinson's disease.