The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects

Background : Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods : Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results : Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions : These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.     

Reduced upper airway nitric oxide in cystic fibrosis

PURPOSE: Incidence data for severe aplastic anaemia (SAA) in children are scanty and vary. Few population based studies have been reported. A retrospective and prospective study was conducted to determine the incidence and course of SAA. PATIENTS AND METHODS: All children with a diagnosis of SAA in the Nordic countries from 1982 through 1993 were registered and have been followed up since 1987. RESULTS: A total of 101 children were diagnosed with SAA. The mean annual child population was 4.31 million. A constant incidence of 1.95/million children/year was found: 2.4 for boys and 1.5 for girls. A non-significant increase of cases occurred from November to March. Possible aetiological agents were noted in 29%. The actuarial survival was 79% after one year and 68% after five years without significant difference between boys and girls. CONCLUSION: The incidence of SAA in the Nordic countries remains stable with a preponderance among boys. SAA has still a high initial mortality and a risk of late deaths.     

Late effects of radiotherapy on hearing

Summary The effect of radiotherapy on hearing was studied in 30 patients who were treated by surgery and radiotherapy for a parotid neoplasm. Functions of the irradiated ear were compared with those of the non-irradiated ear in the same patient. Tympanometry showed a small but significant reduction of static compliance on the irradiated side when compared with the non-irradiated side. Audiometry showed a significant increase in hearing loss in the 1–2, 4–8 and 10–20 kHz ranges that increased with frequency. This hearing loss was mainly sensorineural in contrast to hearing loss at 250–500 Hz, where it was more of a conductive type. There appeared to be a significant dose-effect relation in sound perception at 4–8 kHz. Doses to the cochlea of less than 55 Gy seldom caused a hearing loss, in contrast to doses exceeding 65 Gy. Overall, radiotherapy was found to cause significant, mainly sensorineural hearing losses, which were partly dose-dependent.     

Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations

Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.     

The development of a prognostic score for patients with parotid carcinoma

BACKGROUND: Understanding of prognostic factors in parotid carcinoma has grown considerably. In particular, clinical tumor staging and histologic classification have been found to be prognostically important. Univariate and multivariate analyses have indicated that other variables, such as age, pain, skin invasion, and facial nerve impairment, are important predictors as well. In an actual patient, some of these factors are present and others are absent. However, a clinical tool incorporating this information, resulting in an individualized prognosis based on the combined effects of present adverse prognostic factors, has never been devised. METHODS: Of a cohort of 168 patients, 151 were evaluated to assess the prognostic value of clinical and pathologic factors in a multivariate proportional hazards analysis. Follow-up ranged from 1 to 278 months (median, 37 months). The end point was tumor recurrence. Identified prognostic factors and their hazard ratios were combined into prognostic scores. RESULTS: Clinical T classification, clinical N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins acted as major factors predicting recurrence. A prognostic score (PS), generated by the weighted combination of the factors present in the individual patient, placed the patient in one of four subgroups with markedly different prognoses. In the subgroups based on the preoperative prognostic score, 5-year recurrence free percentages ranged from 92% (in the group PS1=1) to 23% (in PS1=4). In the subgroups based on the postoperative prognostic score, which took into account the histologic details of the resected specimen, 5-year recurrence free percentages ranged from 95% (in the group PS2=1) to 42% (in PS2=4). CONCLUSIONS: The proposed subgrouping, which is based on the combined effects of key prognostic preoperative and postoperative factors, provides a practical prognostic grouping system for the clinician treating patients with parotid carcinoma.     

The role of cytotoxic T-lymphocytes in the prevention and immune surveillance of tumors— lessons from normal and immunodeficient mice

The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer, a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite. Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance. A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the highest incidence, we concluded that in this model the immune system constituted a 'tumor-suppressive factor' delaying and sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic than tumors from normal mice, resulting in a high rejection rate. CD8+ cytotoxic T cells were found to be indispensable for this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating immunogenic tumor cell variants in the incipient tumor. In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations and hypotheses.     

Granulomatous mastitis: a report of seven cases

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.