The different faces of shared autoimmunity

The concept of shared autoimmunity comprises various forms of disease: rheumatic diseases in several members of the same family, the coincidence of autoimmune rheumatic with non-rheumatic diseases in relatives of patients, the presence of autoantibodies in healthy relatives of autoimmune disease patients, and the development of two or more autoimmune rheumatic diseases in one patient, the so-called overlap syndromes. The genetic and environmental factors that lead to these phenomena interact in a complex fashion and influence the distinct phenotypic characteristics of each patient. In a previous case series, we described 23 Mexican Mestizo patients with overlap syndromes. Interestingly, rhupus tends to develop sequentially while sclerodermatomyositis tends to appear simultaneously. The clinical course of the other overlap syndromes is rather aggressive, although clinical manifestations respond to standard treatment. The second and/or third disease appears while the first one is still active, even with adequate treatment. The distinct course of overlap syndromes may be partially explained by the interplay of environmental factors with genes that predispose to autoimmunity in general and to manifestations of specific diseases. The analyses of genes that will help understand the pathophysiology of these diseases include several MHC complex genes, cytokines, AIRE, and PDCD1 amongst others.     

Comparing fibromyalgia patients from primary care and rheumatology settings: clinical and psychosocial features

The aim of this study was to compare clinical symptoms, perceived health status, health resource use and psychosocial features in fibromyalgia (FM) patients at different health care levels. A total of 315 participants were recruited from primary care (PC) (n = 101) and rheumatology settings (RS) (n = 214). Subjects completed a protocol of clinical features and health resource use, hospital anxiety and depression scale, sickness impact profile, chronic pain self-efficacy scale, multidimensional pain locus of control scale, perceived health competence scale and chronic pain coping inventory. Student’s t test, effect size, and contrast and power test were performed to examine differences between samples. FM patients treated in PC and RS were similar in most variables assessed and only differed significantly in tender points, sleep disturbance, wellness-focused coping strategies and in self-efficacy beliefs. The similarities do not support patient selection through care levels and thus, in the Spanish health care system at least, endorse PC as a reference unit for treatment and questioning the benefits of referring patients to RS.     

The prognostic value of MDM2 overexpression in superficial urothelial bladder carcinoma

The prognostic significance of p53 accumulation and MDM2 overexpression in superficial and papillary urothelial cell carcinoma (UCC) of the bladder has not yet been established. Therefore, MDM2 and p53 protein were investigated focusing on tumour grade and muscularis mucosae invasion in order to identify their prognostic significance. Thirty-five archival UCC were studied by immunohistochemistry using monoclonal antibodies DO7 against p53, and IB10 against MDM2. MDM2 overexpression was observed in 51.4% of the cases. The recurrence rate for patients with MDM2 overexpression was 7.09 fold higher than for those without MDM2 overexpression. p53 accumulation was not related to prognosis. There was no significant difference between low and high grade tumours in regard to MDM2 overexpression and p53 accumulation. pTa cases presented the higher frequency of MDM2 positive cases (66.7%) and a lower frequency of p53 accumulation (33.3%). MDM2 overexpression does not seem to be related to muscular mucosae invasion. Thus, MDM2 status may well be a prognostic marker in superficial urothelial bladder carcinomas.     

The mossy fiber system of the hippocampal formation is decreased by chronic and postnatal but not by prenatal protein malnutrition in rats

We tested in 70-day-old Sprague-Dawley rats, whether malnutrition imposed during different periods of hippocampal development produced deleterious effects on the total reference volume of the mossy fiber system. Animals were treated under four nutritional conditions: (a) well nourished; (b) prenatal protein malnourished; (c) chronic protein malnourished and (d) postnatal protein malnourished. Timm's stained material was used in coronal hippocampal sections (40 microm) to estimate--using the Principle of Cavalieri--the total reference volume of the mossy fiber system in each experimental group. Our results show that chronic and postnatal protein malnourished, but not prenatal malnourished rats, decrease the mossy fiber system and the total reference volume of the mossy fiber system are selectively vulnerable to the type of dietary restriction. Thus, chronic and posnatal protein malnutrition produce deleterious effects, but only rats under prenatal protein malnutrition were able to reorganize synapses in this plexus. These findings raise the possibility that chronic malnutrition, as a long-term stressful factor, might be an important paradigm to test structural hippocampal changes that produce physiological and pathophysiological effects, or the possibility to recover its function for nutritional rehabilitation.     

Postoperative radiochemotherapy in rectal cancer comparison of two combination schemes: alternating versus concomitant

AIMS AND BACKGROUND: To compare the results on disease control and toxicity of two different schedules of adjuvant combined treatment in advanced rectal cancer. METHODS: From January 1995 to September 1998, 127 patients with stage B2-C rectal cancer were treated with postoperative chemotherapy and radiotherapy with two different schemes: three cycles of 5-fluorouracil and leucovorin followed by pelvic radiotherapy and three weeks after radiation therapy was completed, another three cycles of chemotherapy were administered (alternating arm), or two cycles of 5-fluorouracil and leucovorin followed by concurrent radiochemotherapy and three weeks after ending another two cycles of 5-fluorouracil and leucovorin were administered (concomitant arm). RESULTS: Grade 3 acute toxicity was more frequent in the concomitant schedule group (33% vs 13%, P = 0.014). In the alternating schedule group, the acute adverse effects were observed after an average radiation dose of 28.4 Gy and in the concomitant schedule group after an average dose of 22.7 Gy (P = 0.012). In the arm of concomitant treatment, 37.8% of patients had to interrupt the irradiation for severe toxicity compared to 10.4% in the arm of alternating treatment (P = 0.001). There was no difference in the rate of late toxicity. The actuarial overall survival rates at 3 and 5 years were, respectively, 68.8% and 56.6% in the alternating arm and 75.5% and 61.8% in the concomitant arm (P = 0.4599). There were no differences between the two arms in the 5-year actuarial rates of overall recurrence (47% vs 51.3%, P = 0.722), local recurrence (34.6% vs 35.7%, P = 0.935) or distant recurrence (32.7% vs 31.8%, P = 0.983). CONCLUSIONS: For patients with B2-C rectal cancer, postoperative treatment with an alternating scheme of chemoradiotherapy is as effective as a concomitant scheme in control of the disease. The concomitant scheme had a higher incidence, earlier appearance and higher severity of intestinal acute toxicity than the alternating scheme, with a lower completion rate of chemoradiotherapy but without any influence on late toxicity incidence.     

Case report: severe juvenile type paracoccidioidomycosis with hepatitis C

We present the case of a 34-year-old man with previous history of hepatitis C and severe juvenile type of paracoccidioidomycosis characterized by involvement of the reticuloendothelial system, eosinophilia, lung compromise (pleural effusion), retinal hemorrhage, and blood culture positive to Paracoccidioides brasiliensis. The immune evaluation showed four precipitation lines to P. brasiliensis by the double immunodiffusion test. Treatment with amphotericin B and itraconazol resulted in resolution of the disease.     

Quimioterapia de inducción seguida de radioquimioterapia como alternativa a la laringuectomía en el tratamiento del cáncer de cabeza y cuello localmente avanzado

Objective

To evaluate survival in patients with loco-regional advanced head and neck cancer treated with induction chemotherapy and to assess possible larynx preservation in good responders.

Materials and methods

Between December 1997 and June 2000, patients (n=46) diagnosed as having advanced head and neck carcinoma were treated with induction chemotherapy (CT). This was followed by radiotherapy (RT) + CT if there had been complete response (CR) or partial response (RP) >80%; or followed by total laryngectomy and adjuvant RT if CR or PR was <80%.

Results

Of the 46 patients studied, 57 (80%) had CR, 10% had PR and 10% had no response or disease progression (DP). Median survival was 33%, followup was of 50 months during which the overall survival was 36%, disease-free survival (DFS) was 60% and loco-regional control was 51%.

Conclusion

RT-CT resulted in high rates of disease resolution and speech preservation in patients who, traditionally, had poor clinical and functional outcomes.     

HLA study on two Mexican Mestizo families with autoimmune thyroid disease

Several studies have been done regarding the genetic susceptibility to autoimmune thyroid disease, particularly those related to the role of Major Histocompatibility Complex (MHC) genes in the etiology of the disease. In the present study, we report class I and class II MHC haplotypes in nine individuals affected by Hashimoto thyroiditis and Graves' disease who belong to two distinct Mexican families. In one of the families, Hashimoto thyroiditis was associated with the Human Leukocyte Antigen (HLA) HLA-DR3 allele whereas in the other family the disease was associated with homozygosity for the HLA-DR4 (DRB1*0407), HLA-DQ3 (DQB1*0302) haplotype. On the other hand, Graves' disease was found to be associated in one of the families with HLA-DR2 (DRB1*1501) and in the other with homozygosity for the HLA-DR7 (DRB*0701) and HLA-DQ2 (DQB1*0201) haplotype. These results confirm that in Mexicans as in other ethnic groups, genes located within the MHC region are related to the genetic susceptibility to develop autoimmune thyroid disease.