Fetal diagnosis and fetal surgery

Accurate fetal diagnosis became possible by the steadily increasingly complex techniques of amniocentesis, ultrasound, and ultrasound-guided fetal blood sampling and chorion villous sampling. A high degree of diagnostic accuracy for a wide variety of structural and metabolic anomalies is required. The field of fetal diagnosis has been extended to the point that a journal dedicated to this subject alone is a viable proposition. It is becoming apparent, however, that lesions that were well known and well understood when recognized in neonatal life appear in general to have a worse prognosis if the lesion is diagnosed in utero. Fetal surgery began with attempts to perform in utero transfusions for babies with erythroblastosis fetalis. For a while, there was competition between open surgical procedures and the percutaneous placement of blood through catheters introduced into the fetal peritoneal cavity from outside the mother's abdomen. For fetal transfusion, closed techniques proved far safer and just as efficacious. There has been a worldwide interest in shunting of hydrocephalus and obstructive uropathy. The results of shunting hydrocephalus have been disappointing, with most of the patients surviving, but most of the survivors being severely handicapped. The results of shunting obstructive uropathy were that only about 50 per cent of the babies survived, but it appeared that those that did survive did well. Other lesions that have been shunted have been hydrothoraces or fetal ascites. A limited number of open procedures have been carried out in the last few years in San Francisco, and it may well be that diaphragmatic hernia (in appropriately selected patients) will be a lesion that can be corrected by in utero surgery. The future of this field is exciting, but before this form of treatment becomes routine, the ethical implications of the possibility of fetal surgery must be defined much more clearly than is currently the case.     

Concurrent chemoradiation in advanced cervical cancer

The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival.     

Time changes in new cases of ischaemic heart disease in general practice

BACKGROUND: There are no recent studies of the presentation of ischaemic heart disease (IHD) in general practice. What information exists is derived from the secondary care setting, where seasonal and daily variation has been reported in admissions for IHD. There are epidemiological studies that show a falling incidence and mortality for IHD. It is not clear, however, if this is also the case in clinical general practice. OBJECTIVES: The aims of the present study were to (i) estimate the number of cases of IHD in general practice populations; (ii) determine the recorded diagnosis and time of first presentation of IHD during a 5 year period; and (iii) perform time series analysis on the above data. METHODS: The design of the study was a retrospective survey, using MIQUEST software, of computer databases in five general practices with a combined population of nearly 40,000 patients. The five practices were selected randomly from volunteering practices in the Trent Focus Collaborative Research Network. All patients with a new diagnosis of IHD recorded between January 1993 and December 1997 inclusive were included in the study. The number of new cases of IHD, the recorded diagnosis and time of first presentation of IHD were the main outcome measures. RESULTS: A total of 644 new cases of IHD were identified during the study period: 54.0% 'angina pectoris', 26. 9% 'acute myocardial infarction', 18.8% 'ischaemic heart disease', 0. 3% 'coronary atherosclerosis'. Time series analysis reveals a seasonal and weekly pattern to new cases of IHD, with peak cases occurring in January and on Mondays/Fridays. A downward trend was detected for new cases of IHD (all diagnoses) over the 5 year period, and for new cases of IHD (excluding acute myocardial infarction). An upward trend was observed for new cases of acute myocardial infarction. CONCLUSION: Presentation of IHD in general practice varies according to season and day of the week. The proportion of new cases recorded as 'angina pectoris' or 'ischaemic heart disease' is falling, and this decline masks a rise in the incidence recordings of 'acute myocardial infarction'.     

Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery

Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin-C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease-free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures.     

老年性骨质疏松所致骨折患者血清钙磷和TGF-β 1分析

1临床资料2003-06／2004—12收治髋部骨质疏松性骨折患20(男14，女6)例，年龄58—80(平均68．5)岁，股骨颈骨折13例，粗隆间骨折7例．对照组为老年性骨关节病或颈腰椎病患20例．均抽空腹静脉血4mL，3000r／min离心5min分离血清，4h内测定血清钙、磷，留血清-20℃保存备用，测定TGF-β1．用Au-2700全自动生化分析仪测定血清钙、磷，试剂由日本欧林巴斯公司提供．血清TGF-β1检测采用ELISA法，     

Prevention of bronchiolitis

This review evaluates the current situation and long-term prospects for containment of human respiratory syncytial virus (HRSV) infection and bronchiolitis in infancy. The biology and immunopathology of HRSV infection are complex. Initial attempts to control HRSV infection using a conventional formalin-inactivated vaccine had the unexpected outcome that the disease was potentiated in some vaccinees experiencing natural HRSV infection at a later date. Much effort has been devoted to defining the nature of protective immunity, and several candidate sub-unit and live attenuated vaccines have been developed by empirical and semi-empirical routes, and most recently by reverse genetics. None has yet received approval for clinical use, and attention has switched from active to passive immunization. Both concentrated human immune globulin (RespiGam) and a humanized monoclonal antibody (Palivizumab) have been approved for clinical use. On grounds of cost-effectiveness these treatments are recommended only for treatment of high-risk infants. An effective antiviral is not yet available.     

The need for specialist review of pathology in paediatric cancer.

A retrospective histopathological review of 2104 cases of solid tumour was carried out to assess the variability in diagnosis of childhood cancer. Cases were subject to three independent, concurrent opinions from a national panel of specialist pathologists. The conformity between them was analysed using the percentage of agreement and the kappa statistic (kappa), a measure of the level of agreement beyond that which could occur by chance alone, and weighted kappa (w kappa), which demonstrates the degree of variation between opinions. The major groupings of the Birch-Marsden classification were used within which tumours were assigned for kappa analysis according to the clinical significance of the differential diagnoses. The mean agreement for all tumours together was 90%; kappa = 0.82, w kappa = 0.82. Retinoblastoma achieved the highest kappa value (1.0) and lymphoma the lowest (0.66). Of the cases, 16.5% had their original diagnoses amended and the panel confirmed the original diagnosis of paediatric pathologists in 89% of cases compared with 78% for general pathologists. The varying levels of agreement between experts confirm the difficulty of diagnosis in some tumour types, suggesting justification for specialist review in most diagnoses. Specialist training in paediatric pathology is also recommended.     

Secondary thrombocytosis

To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post-operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition.