Recognition of heat shock protein 60 epitopes in children with type 1 diabetes.

BACKGROUND: Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA-DR-binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission. METHODS: Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis. Epitope-specific T-cell proliferation and cytokine production (intracellular and in culture supernatants) were measured. Results were compared with 31 longstanding T1D patients and ten healthy controls. RESULTS: Although HSP60 epitope-specific T-cell proliferative responses were detected, overall proliferative responses were low. At onset, epitope-specific intracellular IFN-γ production was higher in T1D patients compared with healthy controls (p < 0.05). At follow-up, both IL-10 and IFN-γ production were higher in those without a partial remission than in those with a partial remission (both p < 0.05). Also, IL-10 and IFN-γ production were higher compared with onset for patients without a PR (both p < 0.01). In supernatants of HSP60 epitope-specific T-cell cultures, no substantial differences in cytokine production were found between T1D patients with and without a partial remission, either at onset or a few months after onset. As patient numbers were small, results should be interpreted with caution. CONCLUSIONS: Pan-DR-binding HSP60 peptides induced low peptide-specific proliferative responses and peptide-specific production of some, mainly intracellular, cytokines in T1D patients. Recognition did not differ significantly between patient groups and various time points.

Reliability of interpretation of CT examination of the larynx in patients with glottic laryngeal carcinoma.

INTRODUCTION: Reports in literature suggest that tumor volume, cartilage invasion, and cartilage sclerosis are independent prognostic factors for tumor control in radiotherapy as primary treatment of laryngeal carcinomas. OBJECTIVE: Assessment of the interobserver variability and prognostic value in the measurement of tumor volume, cartilage invasion, and sclerosis. MATERIALS AND METHODS: Retrospective analysis of 55 CT scans by three independent observers. Volume measurements and determination of cartilage invasion, cartilage sclerosis, and tumor localization were calculated. Correlation between the prognostic factors and radiotherapy was calculated for each observer. RESULTS: Values for interobserver agreement varied substantially; cartilage invasion (kappa value: -0.02 to 0.66), cartilage sclerosis (kappa value: 0.13 to 0.57), tumor localization of subsites (kappa value: 0.03 to 0.60), and tumor volume (correlation: 0.34 to 0.73). The found interobserver variation makes it impossible to establish accurate prognostic factors. CONCLUSION: Determination of tumor volume, cartilage invasion, and cartilage sclerosis on the basis of CT imaging shows considerable interobserver variation; clinical significance appears to be limited. EBM RATING: B-3a.

Treatment of hypopharyngeal carcinoma: analysis of nationwide study in the Netherlands over a 10-year period.

OBJECTIVE: To analyse different treatment strategies and treatment results of hypopharyngeal carcinoma in the Netherlands. DESIGN: Retrospective study. SETTING: Eight head and neck centres in the Netherlands. PARTICIPANTS: A total of 893 patients were treated between 1985 and 1994. Patients were mostly treated with radiotherapy alone, combined surgery and radiotherapy and surgery alone. RESULTS: The 5-year survival for the whole group was 26%. The 5-year survival for patients treated with curative intention was 32% and treated with palliative intention was 5%. The 5-year disease-free survival after radiotherapy alone was 37%, after surgery alone 41% and after combined therapy 47%. The role of chemotherapy could not be investigated because of a small number of patients treated with chemotherapy in this period. CONCLUSION: Combined therapy with surgery and radiotherapy has a better survival for patients with a hypopharyngeal carcinoma in comparison with radiotherapy alone. The N-stage is more important for the prognosis than the T-stage.

[Trigeminal trophic syndrome: 2 patients with a non-healing ulcer on the ala nasi]. / Het trofisch syndroom van de N. trigeminus: 2 patiënten met een niet-genezend ulcus op de ala nasi.

Two female patients, aged 74 and 91 years respectively, had a skin ulcer on a nostril and ipsilateral sensory paralysis in the area covered by the N. trigeminus. This is known as trigeminal trophic syndrome. It may be caused by (iatrogenic) damage to the trigeminal nerve by chronic manipulation of the senseless skin. Only in case of doubt, histological examination of a tissue sample is advised to exclude malignancy. The main treatment consists of instructing the patient not to manipulate the skin. In some patients surgical reconstruction is necessary.

Metastasizing pleomorphic adenoma: a report of three cases.

Three cases of metastasizing pleomorphic adenoma are described. All three had a history of incomplete surgery of the primary tumour and several surgical procedures for local recurrences before systemic metastases became apparent. The histology of the primary tumour, recurrences and metastases were typical of pleomorphic adenoma. In view of the lack of information in the literature, it is concluded that inadequate surgical procedures, such as incomplete surgery or enucleation, leading to multiple recurrences, appear to be a prerequisite for the development of systemic disease.

Osteoid and bone formation in a nasal mucosal melanoma and its metastasis.

AIMS: To present a literature review and a case history concerning bone and osteoid formation by a metastasizing (mucosal) melanoma. CASE DETAILS: Osteocartilaginous differentiation and production of osteocartilaginous structures in malignant melanoma have been described only in 12 previous cases (osteoid in 11. bone in four), all of which involved dermal melanomas. Five of these melanomas were recurrent and one was associated with neurofibromatosis. The case report concerns a 75-year-old man with a nasal mucosal melanoma which was treated surgically. One year later, the patient developed a local recurrence and a cervical lymph node metastasis. Both the recurrent tumour and the metastasis showed clear evidence of bone and osteoid formation. CONCLUSIONS: This case is the first report in the literature, clearly demonstrating bone and osteoid formation by a mucosal melanoma, not only at the primary site, but even more convincingly in a cervical lymph node metastasis.

Free vascularized jejunum interposition for pharyngoesophageal reconstruction after total laryngopharyngectomy.

The records of 28 patients who underwent free jejunal graft reconstruction after resection for cancer involving the pharynx were analysed. Seven patients had a T3 carcinoma, 15 patients T4 and six patients recurrence after laryngectomy. Ten patients had received radiotherapy in the past. Post-operatively, 15 patients (54%) had complications and two patients (7%) died. No significant difference was observed in the complication rate between the group that received radiotherapy in the past and those who did not. Nineteen patients received post-operative radiotherapy. Nine patients had no radiotherapy on the basis of complete resection or because of serious complications. For the whole group the 2-year recurrence free period and survival were 42% and 51% respectively. The post-operative radiotherapy group had a significantly better survival (73%) and recurrence free period (63%) than the group without post-operative radiotherapy (0%). Thus, post-operative radiotherapy seems indicated irrespective of resection margins.

The ambivalent role of glutathione in the protection of DNA against singlet oxygen.

Glutathione (GSH) was examined with respect to its ability to protect DNA against 1O2 damage. We have found that GSH protected, at least partly, the DNA against inactivation by 1O2. Up to 10 mM the protection increased as a function of GSH concentration. Above 10 mM the protection remained constant and less than expected on the basis of scavenging/quenching of 1O2, in contrast to the protection offered by sodium-azide. Especially at the higher concentrations of GSH the protection against the biological inactivation is accompanied by an increase in single-strand breaks and also probably lethal base damage. However, all together the data suggest that at least in the physiologically important range (0.1-10 mM) GSH is able to protect efficiently against 1O2-induced inactivating DNA damage.