Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects.

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.

Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study.

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress-activated p38 MAPK and JNK signal pathway in H460 cell lines.

AIMS: The purpose of this study was to investigate the photoefficacies of protoporphyrin IX (PpIX) generated by drug precursor 5-aminolevulinic acid (ALA) and its hexyl ester (H-ALA) on two human non-small lung carcinoma cell lines (H460/Bcl-2 and H460/neo). MAIN METHODS: Drug uptake and the photoefficacies of PpIX were measured by flow cytometry and MTT assay; while the mode of cell death and alternation of signal transduction pathways were studied with 4',6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis, respectively. KEY FINDINGS: The flow cytometric analysis of H-ALA (5µM) uptake revealed optimal fluorescent intensity at 8h incubation, while ALA (0.5mM) was still far from saturation. The LD(30) of H-ALA-PDT was 30µM, 2J/cm(2), while the LD(30) of ALA-PDT was 3mM, 2J/cm(2). The dark toxicities mediated by both pro-drug H-ALA and ALA were negligible. By DAPI staining, apoptotic cell death was observed. In addition, by Western blot analysis, H-ALA- and ALA-mediated PDT initiated apoptotic cell death via the up-regulation and activation of p38 mitogen activated protein kinase (MAPK), the stress-activated c-jun N-terminal kinases (JNK) and ERK. SIGNIFICANCE: These results suggested that H-ALA and ALA mediated PDT displayed similar photocytotoxicities towards the two non-small lung cancer cells. Our present study also demonstrates H-ALA or ALA mediated PDT in H460 cells are closely related to the activation of p38 MAPK and JNK signalling pathway.

The use of the Digit Span Test in screening for cognitive impairment in acute medical inpatients.

BACKGROUND: There is no valid instrument currently in use at acute-care hospitals in Hong Kong to aid the detection of cognitive impairment. The objectives of this study were to (1) validate the Digit Span Test (DST) in the identification and differentiation of dementia and delirium; and (2) determine the prevalence of major cognitive impairment in elderly people in an acute medical unit. METHODS: During the study period from January to February 2010, 144 patients aged 75 years or more who had had unplanned medical admissions were assessed by nurses, using the Digit Span Forwards (DSF) and the Digit Span Backwards (DSB) tests. The DST scores were compared with the psychiatrists' DSM-IV-based diagnoses. Receiver Operating Characteristics curve (ROC) was used in conjunction with sensitivity and specificity measures to assess the performance of DST. RESULTS: The prevalence rates of dementia alone, delirium alone and delirium superimposed on dementia were 21.5%, 9% and 9% respectively. The prior case-note documentation rate was 13.2% for dementia and 2.8% for delirium. Regarding the detection of major cognitive impairment, the ROC curve of DSB showed a sensitivity of 0.77 and specificity of 0.78 at the optimal cutoff of <3. A significant association between scores on the DST and the Cantonese version of the Mini-Mental State Examination (CMMSE) was found in this study (p < 0.05 for DSF, p = 0.00 for DSB). CONCLUSIONS: Dementia and delirium were prevalent, yet under-recognized, in acute medical geriatric inpatients. The DSB is an effective tool in identifying patients with major cognitive impairment.

Peri-operative blood transfusion increases length of hospital stay and number of postoperative complications in non-cardiac surgical patients.

OBJECTIVES: To test the hypothesis that blood transfusion alone was a significant risk factor for in-hospital morbidity in non-cardiac patients. DESIGN: Propensity analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive non-cardiac patients seen in our department from 2006 to early 2009 who underwent a major procedure under general or spinal anaesthesia were included. Propensity analysis was performed to neutralise the confounding effects of preoperative variables and identify the true effects of transfusions on surgical outcomes. MAIN OUTCOME MEASURES: Receipt of intra-operative and postoperative blood transfusion was established and the difference in proportions between patients who did and did not receive donor blood tested for mortality, overall morbidity, individual complications, and number of adverse events. RESULTS: Transfused patients were significantly older and sicker, more likely to be male, to have lower haemoglobin values and undergo longer and more emergency surgical procedures than those not receiving a transfusion. Blood transfusion was predictive of length of postoperative hospital stay and number of complications before discharge. The amount of transfused blood was predictive of in-hospital mortality, with an odds ratio of 1.4 for each unit of blood received. The risk of a surgical wound infection was almost doubled when the patient had received a blood transfusion. CONCLUSION: After controlling for the factors associated with an increased likelihood for receiving a blood transfusion, the actual transfusion was predictive of a slower and more eventful postoperative recovery with associated costs to both the patient and health services.

Subfascial endoscopic perforator surgery for venous ulcers.

We report the treatment and outcomes of 12 patients who underwent subfascial endoscopic perforator surgery for severe chronic venous insufficiency and venous ulceration. All patients had received prior superficial venous ablative surgery and presented with incompetent perforating veins in the calf and persistent venous ulceration (lasting >10 years). Outcome measures included ulcer healing time, recurrence, clinical symptom, and disability scores. There was one wound complication after subfascial endoscopic perforator surgery. The cumulative ulcer healing rate was 25% at 3 months, 42% at 6 months, and 92% at 1 year. One patient developed ulcer recurrence at 12 months after surgery. The mean clinical score and disability score decreased from 13.00 (standard deviation, 2.26) to 4.83 (1.47) and 1.75 (0.45) to 0.50 (0.52), respectively (P<0.001) after a median follow-up of 15.0 months (interquartile range, 12.0-21.5 months). Subfascial endoscopic perforator surgery was safe and effective in the treatment of patients with severe chronic venous insufficiency and venous ulceration caused by incompetent perforating veins in the calf.

Solid-state NMR conformational studies of a melittin-inhibitor complex.

Melittin is a cytolytic peptide whose biological activity is lost upon binding to a six-residue peptide, Ac-IVIFDC-NH(2), with which it forms a highly insoluble complex. As a result, the structural analysis of the interaction between the two peptides is difficult. Solid-state NMR spectroscopy was used to study the interaction between melittin and the peptide inhibitor. Location of the binding site in the melittin-inhibitor complex was determined using lanthanide ions, which quench NMR resonances from molecular sites that are in close proximity to the unique ion binding site. Our results indicated that the inhibitor binding site in melittin is near Leu13, Leu16 and Ile17, but not near Leu6 or Val8. On the basis of these data we propose that the inhibitor binds to melittin in the vicinity of Ala15 to Trp19 and prevents insertion of melittin into cell membranes by disrupting the helical structure. Supporting evidence for this model was produced by determining the distance, using rotational resonance NMR, between the [1-(13)C] of Leu13 in melittin and the [3-(13)C] of Phe4 in the inhibitor.

The clinical efficacy of neoadjuvant chemotherapy in squamous esophageal cancer: a prospective nonrandomized study of pulse and continuous-infusion regimens with Cisplatin and 5-Fluorouracil.

BACKGROUND: We evaluated cisplatin and 5-fluorouracil as preoperative adjuvant chemotherapy for patients with locally advanced squamous esophageal cancer and compared two different infusion regimens. The outcomes were also compared with those of our historical control patients treated by surgery alone. METHODS: From 1991 to 1997, 83 consecutive esophageal cancer patients underwent surgical exploration after completion of two cycles of cisplatin and 5-fluorouracil chemotherapy regimens, either in pulse or in continuous infusion cycles. Outcomes were compared with those of 76 historical control patients. Both groups were comparable in demographic characteristics and tumor stages. The resection rates, operative morbidity, mortality, and survival rates were compared. RESULTS: Partial response was achieved in 50% of patients who received chemotherapy. There was no chemotherapy-related mortality. The resection, morbidity, and mortality rates and median survival between the surgery-alone group and the chemotherapy group were 71.1% vs. 82%, 51% vs. 55%, and 4% vs. 10.8%, 12.0 vs. 13.5 months, respectively (P >.05). There was also no statistically significant difference between the two regimens. CONCLUSIONS: Preoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil infusion, in pulse or continuous regimens, followed by surgery for squamous esophageal cancer patients had no added benefit in the overall survival.

Early clinical outcomes after subfascial endoscopic perforator surgery (SEPS) and saphenous vein surgery in chronic venous insufficiency.

BACKGROUND: Subfascial endoscopic perforator surgery (SEPS) has recently become popular as a minimally invasive way to treat chronic venous insufficiency (CVI) of the lower extremities. We report the early clinical outcomes of SEPS and saphenous vein surgery in a prospective series of Chinese patients who presented with severe CVI. METHODS: All patients referred to our hospital for the management of severe CVI (class IV disease or above) after January 1998 underwent SEPS using an ultrasonic scalpel in conjunction with saphenous vein surgery. All patients were followed up prospectively to assess ulcer healing, ulcer recurrence, and symptoms after SEPS. Clinical outcome was evaluated by the scoring system suggested by the Consensus Committee of the American Venous Forum on Chronic Venous Disease. RESULTS: Over a 24-month period, we performed 36 SEPS on 31 patients. Nineteen lower extremities (53%) had active or healing ulcers. Sapheno-femoral ligation was also performed in 33 limbs (92%). Four limbs (11%) developed superficial wound infection, and two (6%) had saphenous nerve dysesthesia. The mean clinical score and disability score decreased from 8.42 to 3.42 and 1.45 to 0.31 respectively, after a median follow-up of 14 months (range, 6-22) (p < 0.005). Eleven ulcers (58%) healed within 6 weeks after surgery. At 1-year follow-up, ulcer recurrence was found in two legs (11%). CONCLUSION: SEPS is safe and feasible. Early clinical results have shown a promising outcome in patients with severe chronic venous insufficiency.

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.

Subfascial endoscopic perforator vein surgery (SEPS) using the ultrasonic scalpel.

Subfascial endoscopic perforator vein surgery (SEPS) was recently introduced as a minimally invasive method to ligate incompetent perforating veins in patients with severe chronic venous insufficiency of the lower extremities. Herein we describe a technique in which we used a 5-mm ultrasonic scalpel for the transection of perforating veins in 16 SEPS performed in 14 patients. The use of the ultrasonic scalpel allowed for the precise coagulation and transection of the perforator vein with hemostasis, while avoiding the use of metal clips. Our initial results showed that the technique was feasible with minimal morbidity. We recommend the use of the ultrasonic scalpel as an alternative tool to transect perforating veins in SEPS.

Acceptability of serum screening as an alternative to cytogenetic diagnosis of down syndrome among women 35 years or older in Hong Kong.

The addition of second trimester serum markers to maternal age increases the efficacy of screening for Down syndrome by maternal age alone. Among women aged 35 years or older, serum screening makes a large proportion of amniocentesis unnecessary. However, there are ethical and medicolegal concerns about serum screening in 'old' women, largely because some of the pregnancies affected by Down syndrome and other chromosomal abnormalities may not be detected. We investigated the acceptability of serum screening in women aged 35 years or older when it was offered as an alternative to prenatal cytogenetic diagnosis after detailed counselling. Women referred for prenatal diagnosis of Down syndrome because of advanced maternal age were given the options of cytogenetic diagnosis by chorionic villus sampling (CVS) or amniocentesis. As an alternative, they could choose to undergo second trimester serum human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) screening first before deciding on whether to undergo amniocentesis. Between January 1997 and October 1999, 3419 subjects were recruited. 1807 women (52. 9%) chose to undergo serum screening, 1516 women (44.3%) chose to have amniocentesis and 96 women chose to have CVS (2.8%). The proportion of women who chose serum screening rose steadily from 38. 8% in the year of 1997 to 63.4% in 1999. Significantly fewer Chinese women chose serum screening than non-Chinese. The decision as to whether to undergo an invasive diagnostic procedure or to be content with the relatively safer but less accurate screening test varies, being affected by the women's background and culture.

Diagnostic and therapeutic fistuloscopy: an adjuvant management in postoperative fistulas and abscesses after upper gastrointestinal surgery.

BACKGROUND AND STUDY AIMS: Postoperative fistulas and abscesses pose difficult management problems. We report our experience in the use of fistuloscopy in postoperative fistulas and abscesses after upper gastrointestinal surgery. PATIENTS AND METHODS: From June 1993 to January 1997, nine patients (seven men, two women; mean age 65) with postoperative fistulas and abscesses were treated with therapeutic fistuloscopy. Diagnostic fistuloscopy was carried out using a 5-mm choledochoscope under fluoroscopic guidance. Therapeutic procedures included mechanical debridement, irrigation, and sealing of fistula with fibrin sealant and gelatin sponge. RESULTS: The patients were suffering from duodenal stump fistula (three cases), gastrojejunostomy dehiscence after gastrectomy (three cases), gastropleurocutaneous fistula (two cases), and subphrenic abscesses (two cases). Fistuloscopy was performed 4-19 days (mean 12 days) after the diagnosis of the fistula. The median number of sessions required was 2 (range 1-4). The average daily fistula output prior to fistuloscopy was 154 ml (range 30-560 ml), and all fistulas healed in an average of 18.7 days (range 2-46 days) after index fistuloscopy. No procedure-related complications occurred. The mean hospital stay was 61 days. During a mean follow-up period of 12 months, no recurrent abscesses or fistulas developed. CONCLUSIONS: Fistuloscopy provides a new means of managing patients with postoperative fistula and abscess formation.

Eradication of Helicobacter pylori prevents recurrence of ulcer after simple closure of duodenal ulcer perforation: randomized controlled trial.

OBJECTIVE: In this randomized trial, the authors sought to determine whether eradication of Helicobacter pylori could reduce the risk of ulcer recurrence after simple closure of perforated duodenal ulcer. BACKGROUND DATA: Immediate acid-reduction surgery has been strongly advocated for perforated duodenal ulcers because of the high incidence of ulcer relapse after simple patch repair. Although H. pylori eradication is now the standard treatment of uncomplicated and bleeding peptic ulcers, its role in perforation remains controversial. Recently a high prevalence of H. pylori infection has been reported in patients with perforations of duodenal ulcer. It is unclear whether eradication of the bacterium confers prolonged ulcer remission after simple repair and hence obviates the need for an immediate definitive operation. METHODS: Of 129 patients with perforated duodenal ulcers, 104 (81%) were shown to be infected by H. pylori. Ninety-nine H. pylori-positive patients were randomized to receive either a course of quadruple anti-helicobacter therapy or a 4-week course of omeprazole alone. Follow-up endoscopy was performed 8 weeks, 16 weeks (if the ulcer did not heal at 8 weeks), and 1 year after hospital discharge for surveillance of ulcer healing and determination of H. pylori status. The endpoints were initial ulcer healing and ulcer relapse rate after 1 year. RESULTS: Fifty-one patients were assigned to the anti-Helicobacter therapy and 48 to omeprazole alone. Nine patients did not undergo the first follow-up endoscopy. Of the 90 patients who did undergo follow-up endoscopy, 43 of the 44 patients in the anti-Helicobacter group and 8 of the 46 in the omeprazole alone group had H. pylori eradicated; initial ulcer healing rates were similar in the two groups (82% vs. 87%). After 1 year, ulcer relapse was significantly less common in patients treated with anti-Helicobacter therapy than in those who received omeprazole alone (4.8% vs. 38.1%). CONCLUSIONS: Eradication of H. pylori prevents ulcer recurrence in patients with H. pylori-associated perforated duodenal ulcers. Immediate acid-reduction surgery in the presence of generalized peritonitis is unnecessary.

Sonographic diagnosis of congenital megalourethra at 13 weeks of gestation.

Congenital megalourethra is a rare disorder characterized by the congenital absence of the corpus spongiosum and/or corpus cavernosum, leading to dilatation of the urethra. We present a case of congenital megalourethra diagnosed by ultrasound examination at 13 weeks of gestation. Transabdominal and transvaginal sonography showed gross megacystis, bilateral hydronephrosis and a cystic dilatation of the penis. Transabdominal needle embryoscopy confirmed a balloon dilatation of the fetal penis. The pregnancy was terminated by suction curettage.

Conformational studies of a melittin-inhibitor complex.

The conformation of a melittin-inhibitor complex was studied by solution NMR, solid-state NMR, and circular dichroism. In solution, binding was studied by titrating inhibitor against melittin in dimethyl sulfoxide, methanol, aqueous buffer, and dodecylphosphocholine micelles. The change in chemical shift of Trp19 resonances and the formation of a precipitate at 1:1 molar ratio indicated that the inhibitor was bound to melittin. Solid-state NMR also showed a change in chemical shift of two labeled carbons of melittin near Pro14 and a change in 1HT1 relaxation times when complexed with inhibitor. Rotational resonance experiments of melittin labeled in the proline region indicated a change in conformation for melittin complexed with inhibitor. This observation was also supported by circular dichroism measurements, indicating a reduction in alpha-helical structure for increasing ratios of inhibitor bound to melittin.

Risk of neural tube defects in the offspring of thalassaemia carriers in Hong Kong Chinese.

The risk of having an offspring with neural tube defect is negatively correlated with early pregnancy maternal folate levels. Thalassaemia carriers often have subnormal folate levels. We postulate that their offspring may be at increased risk of having neural tube defect. We retrospectively reviewed the records of 1961 Chinese women referred to a tertiary centre for prenatal diagnosis between January 1997 and August 1998. Women with a mean corpuscular volume greater than 80 fl were assumed not to be alpha-thalassaemia-1 or beta-thalassaemia heterozygotes. alpha- and beta-thalassaemia heterozygotes were diagnosed by haemoglobin studies. Of the 1961 women studied, pregnancy outcome was not available in 20 and thalassaemia screening was not available in 109 and these were excluded from the final analysis. Two-hundred-and-six women were alpha-thalassaemia-1 heterozygotes, 102 women were beta-thalassaemia heterozygotes and one woman had HbE disease. Three alpha-thalassaemia carriers and one beta-thalassaemia carrier had a pregnancy affected by anencephaly (odds=1:76). In the 1523 non-carriers, five pregnancies were affected by spina bifida (odds=1:304). The odds ratio (95 per cent confidence interval) for neural tube defects in the alpha- and beta-thalassaemia carriers was 3.99 (1.07 to 14.94; p<0.05, Chi-square test). Because of the small number of affected pregnancies studied, the finding needs to be substantiated by a larger series. If the increased risk is genuine, women need to be screened for thalassaemia before conception and the thalassaemia carriers should be given periconceptional folate supplement to reduce the occurrence of neural tube defects.

Echogenic bowel in fetuses with homozygous alpha-thalassemia-1 in the first and second trimesters.

OBJECTIVE: Fetal echogenic bowel has been observed in fetuses with meconium peritonitis, cystic fibrosis, aneuploidy, congenital viral infection and intrauterine growth restriction. The pathogenesis of echogenic bowel is unknown, but it may be attributed to bowel ischemia. Fetuses affected by homozygous alpha-thalassemia-1 are severely anemic and hypoxic. We investigated the incidence of echogenic bowel in these hypoxic fetuses in the first and second trimesters. DESIGN: Prospective observational study. SUBJECTS: Women referred for the prenatal diagnosis of homozygous alpha-thalassemia-1 before 24 weeks' gestation. METHODS: All subjects had one or more abdominal and/or vaginal ultrasound examination between 12 and 24 weeks' gestation. Echogenic bowel was diagnosed if the bowel appeared either isoechogenic or more echogenic than the bone. RESULTS: Between March 1997 and July 1998, 126 pregnancies were studied. Thirty-six fetuses were confirmed to be affected by homozygous alpha-thalassemia-1, and 11 of them (31%, 95% CI 16-48%) had echogenic bowel. These observations were made before the invasive test results were available. None of the fetuses unaffected by homozygous alpha-thalassemia-1 had echogenic bowel. CONCLUSION: There is a strong association between homozygous alpha-thalassemia-1 and echogenic bowel. The pathogenesis is unknown. Speculations include bowel hypoperistalsis or bowel wall edema due to severe anemia and hypoxia.

Self-expandable metal stents for malignant dysphagia.

BACKGROUND: The use of self-expandable metal stents in relieving dysphagia for patients with incurable malignant oesophageal strictures was retrospectively evaluated. METHODS: Between September 1993 and August 1996, 66 male and 16 female patients with a median age of 72 years received self-expandable metal stents for malignant dysphagia. Six patients had concurrent tracheo-oesophageal fistulas. All patients were stented under sedation and stent insertion was performed under fluoroscopic guidance. RESULTS: Stent placement was successful in 80 patients (98%). There were seven early complications (inaccurate positioning (n = 3), migration (n = 1), incomplete expansion (n = 1), intractable pain (n = 1), and perforation (n = 1)). Two complications were lethal and three were treated endoscopically. Mean dysphagia grade improved from 3.2+/-0.7 to 1.8+/-0.9 (P < 0.05) after implantation. All tracheo-esophageal fistulas were successfully occluded. Upon a median follow-up of 8 weeks (range: 2-20 weeks), 30 complications developed in 21 patients (tumour overgrowth (n = 15), food bolus obstruction (n = 7), tumour ingrowth (n = 2), buckling of stent (n = 2), tracheo-esophageal fistula (n = 2), bleeding (n = 1), and gastric wall herniation through metal coils (n = 1)). Median survival was 13 weeks (range: 1-82 weeks). CONCLUSION: Self-expandable metal stents provide useful palliation in patients with incurable malignant dysphagia.

Cardiac blood flow studies in fetuses with homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 develop anemia as early as the first trimester. Our objective was to study hemodynamic indices in affected fetuses at 12-13 weeks of gestation to determine whether these would be useful in the prediction of anemia. DESIGN: Prospective observational study. SUBJECTS: Women referred before 14 weeks of gestation for the prenatal diagnosis of homozygous alpha-thalassemia-1. METHODS: Transabdominal and/or transvaginal Doppler sonography was performed to measure the flow velocities in the fetal ascending aorta and pulmonary artery at 12-13 weeks. The Doppler indices were compared between those that were subsequently confirmed to be affected by homozygous alpha-thalassemia-1 and those that were unaffected. RESULTS: Between June 1997 and April 1998, 60 eligible women were recruited. Doppler examination was successful in 58 fetuses. Of these, 22 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. The diagnosis was made by chorionic villus sampling and DNA analysis in two affected fetuses and by cordocentesis and hemoglobin evaluation in 20 affected fetuses. Hemoglobin concentrations could be measured in ten fetuses and these ranged from 4 to 8 g/dl. The affected fetuses had significantly higher peak velocities at the pulmonary valve and ascending aorta and a larger inner diameter of the pulmonary valve than that in unaffected fetuses. The total cardiac output was increased by one-third in affected fetuses and was mainly due to an increase of the right-side cardiac output. CONCLUSION: In the early stage of anemia, the fetus responds mainly by increasing its right-side cardiac output. However, there is extensive overlap of the values of cardiac output between the affected and the unaffected fetuses, precluding its use in the prediction of anemia.