Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma in cervical lymph nodes: comparison with metastatic squamous-cell carcinoma,and Hodgkin's and non-Hodgkin's lymphoma

Our objective was to study the cytomorphological features of metastatic nasopharyngeal carcinoma (NPC) as compared to squamous-cell carcinoma (SCC) of nonnasopharyngeal origin, Hodgkin's lymphoma (HL), and non-Hodgkin's (NHL) lymphoma in the neck lymph nodes. The aim of this study was to find simple cytological criteria using routine stains that can help in differentiating between these entities. All fine-needle aspiration (FNA) smears of metastatic NPC, SCC, HL, and NHL from neck nodes available in our files were included in this study. Nodal disease was the first clinical manifestation in all cases of NPC, and all the lesions were of the nonkeratinizing type. The cytomorphological features of metastatic NPC, SCC, HL, and NHL have been described. Metastatic NPC and HL had a similar reactive lymphoid background, with eosinophils, plasma cells, and sometimes epithelioid-cell granulomas. The bizarre cells of NPC showed some resemblance to Reed-Sternberg cells of HL. However, the latter can be distinguished from the former on the basis of bulky, pale gray, vacuolated cytoplasm and vesicular nuclei with sharply demarcated prominent macronucleoli. In NPC, the neoplastic cells form distinct aggregates contrasting with the normal lymphoid cells in the background, which was different from the monotonous dispersed population of cells in NHL. Moreover, bizarre cells, prominent nucleoli, and the presence of plasma cells, eosinophils, and granulomas were not common features of NHL. The smears of metastatic SCC revealed keratinized malignant cells in all cases, while eosinophils and plasma cells were absent in the background. Plasma cells were seen intimately related to tumor cells in all cases of NPC. In conclusion, metastatic NPC can be differentiated from metastatic SCC of nonnasopharyngeal origin, HL, and NHL on the basis of simple nuclear and cytoplasmic features of malignant cells and their background. The presence of plasma cells intermingling with tumor-cell clusters is a good indicator of nasopharyngeal origin. On the other hand, a nasopharyngeal origin is unlikely in the presence of keratinized malignant cells.     

Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations

We describe and functionally characterize six mutations of the acetylcholine receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome patients. Endplate studies demonstrated severe endplate AChR deficiency, dispersed endplate regions and well preserved junctional folds in all three patients. Electrophysiologic studies were consistent with expression of the fetal gamma-AChR at the endplates in one patient, prolongation of some channel events in another and gamma- AChR expression as well as some shorter than normal channel events in still another. Genetic analysis revealed two recessive and heteroallelic epsilon subunit gene mutations in each patient. One mutation in each (epsilonC190T [epsilon R64X], epsilon 127ins5 and epsilon 553del 7) generates a nonsense codon that predicts truncation of the epsilon subunit in its N-terminal, extracellular domain; and one mutation in each generates a missense codon (epsilon R147L, epsilon P245L and epsilon R311W). None of the mutations was detected in 100 controls. Expression studies in HEK cells indicate that the three nonsense mutations are null mutations and that surface expression of AChRs harboring the missense mutations is significantly reduced. Kinetic analysis of AChRs harboring the missense mutations show that epsilon R147L is kinetically benign, epsilon P245L prolongs burst open duration 2-fold by slowing the rate of channel closing and epsilon R311W shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation. The modest changes in activation kinetics are probably overshadowed by reduced expression of the missense mutations. The consequences of the endplate AChR deficiency are mitigated by persistent expression of gamma-AChR, changes in the release of transmitter quanta and appearance of multiple endplate regions on the muscle fiber.      

Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome

The concentrations of endometrial proteins PP14 and CA-125 were measured in uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile women and 49 women who suffered recurrent miscarriage. The concentration of PP14 was significantly lower in the flushings from the recurrent miscarriage patients than in those from fertile controls on both day LH+10 (median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40 404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly concentrations of CA-125 were significantly lower in flushings from recurrent miscarriage women compared to controls on both day LH + 10 (median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731 U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there was no significant difference in the concentration of PP14 in plasma samples taken on the same days as the flushings from recurrent miscarriage patients and fertile controls. The concentrations of PP14 in uterine flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage women during a pre-pregnancy investigative cycle were significantly lower (P < 0.05) in patients who went on to miscarry (median: 1000, range: 9-2900 ng/ml) than those who went on to have a live birth (median: 1440, range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was no significant difference in uterine CA-125 or plasma PP14 concentrations between these two groups of recurrent miscarriage patients. The results suggest that measurements of uterine PP14 and CA-125 may be useful in the assessment of endometrial development in recurrent miscarriage patients and suggest the importance of PP14 in preparing the endometrium for embryo implantation. In addition pre-pregnancy uterine PP14 measurements may be useful in predicting subsequent pregnancy outcome.      

Serotonin transporter (5-HTT) gene variants associated with autism?

An association study was performed to elucidate the role of the serotonin transporter (5-HTT) gene as a susceptibility factor for autism as treatment of patients with antidepressant drugs which selectively target 5-HTT reduced autistic or concomitant symptoms, such as repetitive behavior and aggression, and ameliorate language use. Using the transmission/disequilibrium test (TDT) an analysis was done for a common polymorphism in the upstream regulatory region (5-HTTLPR), a VNTR in intron 2 of the gene and a haplotype of both loci in 52 trios fulfilling stringent criteria for autism and an extended group of 65 trios including patients showing no language delay in their first 3 years of life. A higher frequency and preferential transmission of the long allele of the 5-HTTLPR was observed, but the TDT gave a statistically significant value ( P = 0. 032) only for the extended patient group. This result is in contrast to a recent study by a US group presenting preliminary evidence for preferential transmission of the short allele of 5-HTTLPR in 86 trios. Both studies failed to reveal significant linkage disequilibrium between the VNTR in intron 2 of the gene and autism. In our study haplotype analysis of the 5-HTTLPR and the VNTR in intron 2 supplied evidence for an association of 5-HTT and autism in the stringent ( P = 0.069) and extended patient group ( P = 0.049). Overall, we were not able to replicate the findings of the first study on 5-HTT and autism and instead observed a tendency for association of the opposite genetic variant of the gene with the disorder. The implications for genetic variants of the serotonin transporter in the etiology of autism and possible subgroups of patients, therefore, needs clarification in further studies with other and larger patient samples.      

Extrauterine placental site trophoblastic tumour in association with a lithopedion

AIM: We describe an unusual case of extrauterine placental site trophoblastic tumour located in pouch of Douglas in association with a lithopedion. METHODS AND RESULTS: A 35-year-old female presented with acute abdomen and peritonitis following rectal perforation. The patient gave a history of 5 months amenorrhoea followed by vaginal bleeding 5 years prior to admission. At laparotomy, a lithopedion was found in pouch of Douglas with rectal perforation and peritonitis. The lithopedion was removed, rectal perforation was sutured and a colostomy was performed. The colostomy was closed later and tumour was seen in the colostomy wound as well as attached to the lithopedion removed previously. The patient presented with a repeated episode of rectal perforation and the tumour had spread to colon, small intestine, omentum, mesentery and right ovary. CONCLUSION: A high-grade malignant placental site trophoblastic tumour with aggressive clinical course occurred at an extrauterine site. It complicated calcified abdominal pregnancy and resulted in repeated rectal perforation and peritonitis.     

Childhood tuberculosis in Malawi: caseload,diagnostic practices and treatment outcomes

There were 22,982 cases of TB registered in Malawi in 1998, of which 2739 (11.9%) were children. Children accounted for 11.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extrapulmonary TB (EPTB). A significantly higher proportion of TB cases were diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. In 2001, all 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB) were surveyed to determine actual diagnostic practice. This cross sectional study identified 150 children aged 14 years or below in hospital receiving anti-TB treatment, 98 with pulmonary TB (PTB) and 52 with extrapulmonary TB (EPTB). Median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a positive family history of TB. Nearly 45% had weight for age < 60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. Diagnostic difficulties make it difficult to accurately define the actual burden of childhood TB in Malawi. Diagnostic practices are poor and treatment outcomes unsatisfactory.     

Catheter-ablative techniques for the treatment of atrial fibrillation

Atrial fibrillation is the most commonly encountered arrythmia in clinical practice and is associated with significant morbidity and mortality. Pharmacologic therapy, although useful for rate control, has proven much less effective in the long term maintenance of sinus rhythm. The utility of implantable atrial defibrillators or pacing to prevent atrial fibrillation remains largely untested. This article describes four catheter-based therapies for atrial fibrillation: His ablation, atrioventricular nodal modification, the Maze procedure, and the ablation of pulmonary vein foci which initiate the arrhythmia. Whereas the first two procedures are largely palliative and recommended for patients with symptomatic, drug-refractory atrial fibrillation, the latter two offer the potential for a curative intervention.     

罗格列酮和二甲双胍对初诊2型糖尿病胰岛素抵抗的影响

目的:观察罗格列酮和二甲双胍对初诊2型糖尿病患者胰岛素抵抗(IR)的影响. 方法:初诊2型糖尿病48例,在饮食和运动治疗基础上随机给予罗格列酮片4 mg 1次/d,即罗格列酮组;给予二甲双胍片500 mg 2次/d,即二甲双胍组,疗程12 wk. 结果:在两组患者取得相当降糖疗效基础上,二甲双胍组和罗格列酮在治疗后空腹和馒头餐后C肽水平均较用药前有明显降低、IR亦有降低、β细胞功能明显改善. 罗格列酮在降低餐后胰岛素、改善IR方面优于二甲双胍,两药物治疗前后血游离脂肪酸水平未见显著差异. 结论:二甲双胍和罗格列酮都可降低IR和改善β细胞功能,在降低IR方面,罗格列酮优于二甲双胍.