Predictive factors of thyroid carcinoma in non-toxic multinodular goitre

The management of nontoxic multinodular goitre (NMNG) remains controversial. The challenge for the clinician is to identify the small proportion of NMNG patients with associated thyroid carcinoma who would thus benefit from surgery. We studied retrospectively the medical records of 80 patients with NMNG and coexisting thyroid carcinoma who underwent total thyroidectomy. Eighty total thyroidectomy patients with NMNG whose histology was benign were then randomnly chosen as controls. In univariate analysis, the following parameters were significantly more frequent in the carcinoma group: rapid growth of the goitre (p = 0.002), presence of microcalcifications (p = 0.01), hypoechogenicity (p = 0.02), firm consistency of a nodule (p = 0.03), and presence of a dominant cold nodule on scintigraphy (p = 0.03). In the multiple regression analysis, the variables significantly associated with carcinoma were rapid growth (Odds ratio (OR) = 4.13, 95% confidence interval(CI): 1.72-9.89), hypo-echogenicity (OR = 3.11, 95% CI: 1.13-8.51) and the presence of a dominant nodule (OR = 2.26, 95% CI: 1.06-4.79)). In the cancer group, tumour size was positively correlated with compression signs (p = 0.01), age (p = 0.02), the presence of a dominant nodule on scintigraphy (p = 0.02), and with rapid growth (p = 0.04). Concerning nodule size estimated on US (ultrasound), the majority (65%) of patients without carcinoma had nodules < 3 cm, whereas 73% of patients with clinical thyroid carcinoma (> or = 1 cm on histology) had nodules with a diameter of > or = 3 cm on US (p = 0.02). In conclusion, our study suggests that surgical treatment of NMNG should be proposed in the presence of rapid nodular growth, compression signs, dominant nodule on scintigraphy, nodule size > or 3 cm and hypo-echogenicity.     

Temporal patterns of the cerebral inflammatory response in the rat lithium-pilocarpine model of temporal lobe epilepsy

To better understand the role of inflammatory responses in temporal lobe epilepsy, we characterized Interleukin1-beta (IL1-beta), Nuclear Factor-kappaB (NF-kappaB), and Cyclooxygenase-2 (COX-2) expression together with neurodegeneration in the rat lithium-pilocarpine model. The immunohistochemical expression of IL1-beta, NF-kappaB, and COX-2 started by 12 h post-injection, persisted for 24 h (status epilepticus period), and returned to basal levels by 3 and 6 days (latent period). The regional distribution of IL1-beta, NF-kappaB, and COX-2 occurred mainly in structures prone to develop neuronal damage. Using double-staining protocols, we detected IL1-beta expression in glial cells, COX-2 expression in neurons, and NF-kappaB in both cell types. The presence of Fluoro-Jade-B-positive degenerating neurons was associated with IL1-beta, NF-kappaB, and COX-2 proteins expression during status epilepticus but not during the latent period while neurons were still degenerating. These data suggest that seizure-related IL1-beta, NF-kappaB, and COX-2 expression may contribute to the pathophysiology of epilepsy by inducing neuronal death and astrocytic activation.     

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

Introduction  

Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability.     

Ligands of the peripheral benzodiazepine receptor have therapeutic effects in pneumopathies in vivo

In this study, we documented the effects of different peripheral benzodiazepine receptor (PBR) ligands: PK 11195, Ro5-4864 and the newly described SSR 180575 on the development of pulmonary inflammation in vivo. To this aim, we used MRL/lpr mice that develop pathological signs similar to the human lupus erythematosus (LE) signs. We found that a chronic treatment (at 3 mg/kg per i.p. for 30 days) with PBR ligands had a significant beneficial therapeutic action and decreased the inflammatory pulmonary responses and alveolitis onset. When analyzing PBR expression in inflamed tissues, we observed that in addition to the infiltrated leukocytes, PBR was expressed in the bronchial epithelium, and especially we evidenced for the first time that PBR in expressed in Clara cells. Interestingly, we observed that PBR expression in those cells was reduced when MRL/lpr mice developed the pathology and restored upon PBR ligand treatment. These original findings support a role of PBR in pulmonary inflammatory process and suggest new therapeutic applications in auto immune disorders for specific potent PBR ligands.     

Frozen section examination of the endocervical margin of cervical conization specimens

OBJECTIVE: We conducted this retrospective study to determine accuracy of frozen section examination of endocervical margin during cold knife conization. METHODS: Between June 1993 and June 2001, 310 consecutive patients underwent cervical conization for squamous intraepithelial lesion or stage IA1 cervical cancer. Before 1997, the surgical specimens of 149 patients were processed following a standard pathological procedure (historical group). After 1997, a frozen section of the upper endocervical margin was processed during surgery for 161 patients. If the upper endocervical margin was involved with intraepithelial neoplasia, the surgeon performed a second resection if possible. Results of the frozen section examination were compared with the final diagnoses to determine sensitivity, specificity, and positive and negative predictive values. The usefulness of this procedure was evaluated by comparison of positive margin status rate with the one of the historical control group. RESULTS: For the diagnosis of intraepithelial neoplasia involving the endocervical margin, the sensitivity, specificity, and positive and negative predictive values of frozen section were 91%, 100%, 100%, and 98%, respectively. Eleven patients had definitive positive endocervical margin in the frozen section group (three false negatives, six patients without additional resection, and two patients with intraepithelial neoplasia involving the upper margin of the additional resection) and 17 patients in the historical group (P =.16). CONCLUSION: Frozen section examination of the endocervical margin of cervical specimen obtained during cold knife conization is highly accurate. Its clinical relevance has to be demonstrated in a multicenter study.     

TP53 polymorphism at exon 4 in caucasian women from eastern France: lack of correlation with HPV status and grade of cervical precancerous lesions

OBJECTIVE: To investigate the codon 72 TP53 polymorphism in women from eastern France with normal or abnormal cervical cytology.STUDY DESIGN: We analyzed the TP53 allele distribution by denaturant gradient gel electrophoresis assay and the human papillomaviruses (HPV) infection in 138 cervical smears: 50 normal, 20 atypical squamous cells of undetermined significance, 40 low grade squamous intraepithelial lesions, 28 high grade squamous intraepithelial lesions.RESULTS: The viral DNA prevalence increased with cytological abnormalities. The rates of arginine (Arg) and proline (Pro) homozygosity and Arg/Pro heterozygosity were 49, 0.72, and 51%, respectively. No association was found between HPV status and TP53 polymorphism. No differences were observed in the frequency of the TP53 genotypes according to cytology.CONCLUSION: The TP53 Arg/Arg genotype does not appear to represent a risk factor in the progression of HPV associated cervical lesions. We were not able to confirm that the TP53 genotype increases the susceptibility to be infected by HPV or to develop HGSIL, and a fortiori invasive carcinoma of the cervix.     

Musculoskeletal manifestations in cystic fibrosis

Although bone and joint manifestations are common in children with cystic fibrosis (CF), they have received little attention in adults. As compared to healthy individuals, bone mineral density is low, even with calcium intakes greater than 1500 mg/d. Nevertheless, calcium and phosphate levels in blood and urine are often normal, and vitamin D levels vary. Short stature with a low body mass index and central hypogonadism are the rule in these patients. Fractures and kyphosis are often reported. CF arthropathy occurs in 2-8.5% of patients. Arthritis develops, and there may be skin eruptions. Non-steroidal antiinflammatory drug therapy is effective. Hypertrophic osteoarthropathy associated with respiratory failure is present in 2-7% of patients. Rheumatoid arthritis, spondyloarthropathies, sarcoidosis, and amyloidosis have been reported in association with CF. Knee pain due to patellofemoral syndrome, quinolone-induced arthropathy, and mechanical back pain have been described. Rheumatoid factor titers are higher than in healthy controls, particularly in patients with episodic arthritis. No data are available on antiperinuclear factor or antikeratin antibody titers. Tests for antinuclear antibody are usually negative. Circulating immune complex levels and antibodies to heat shock proteins may be elevated. Antineutrophil cytoplasmic antibody of the bactericidal/permeability-increasing protein (BPI) or azurocidin (AZ) type has been reported, often in high titers (up to 40%).