Early sonographic diagnosis of body stalk anomaly

Ultrasonographic features of a fetus at 18 weeks of gestation suggesting a body stalk anomaly are presented. These included a large abdominal anterior wall defect in apparent continuity with the placenta, severe kyphoscoliosis of the lower spine, the absence of one kidney, and a very short umbilical cord with only one umbilical artery. The amniotic fluid was reduced and the fetus was almost immobile at short-interval ultrasound examinations. The pregnancy was terminated and autopsy of the fetus showed abnormalities compatible with maldevelopment of both cephalic and caudal embryonic folds.     

Enhancement of tumor-specific immune response with plasmid DNA replicon vectors

To enhance the immunogenicity of nucleic acid vaccines, we used plasmid DNA vectors that contained replicons derived from the prototype alphavirus, Sindbis, and another alphavirus, Semliki Forest virus. When transfected into cells or injected directly into animal muscle, these plasmids launch a self-replicating RNA vector (replicon) which in turn directs the expression of a model tumor antigen. Immunization with plasmid DNA replicons elicited immune responses at doses 100 to 1000-fold lower than conventional DNA plasmids and effectively treated mice bearing an experimental tumor expressing the model antigen. Significantly, replicon-based DNA plasmids did not produce a greater quantity of antigen; instead, antigen production differed qualitatively. Plasmid DNA replicons mediated antigen production that was homogeneous in all transfected cells and associated with the apoptotic death of the host cells. Because of their safety and efficacy, plasmid DNA replicons may be useful in the development of recombinant vaccines for infectious diseases and cancer.     

Laser-assisted low-dose retinoic acid in oral cancer chemoprevention

OBJECTIVES: Systemic retinoic acid (RA) treatment for chemoprevention of squamous cell carcinoma of the head and neck (HNSCC) is limited by RA's toxic side effects at therapeutic doses. The pulsed-dye laser (PDL), through a mechanism of selective vascular targeting, may allow reduction of the RA dose to one that is better tolerated when these treatments are used in combination. This study tests our hypothesis that combination therapy of PDL irradiation and low-dose systemic RA is as effective as high-dose RA therapy alone in the chemoprevention of HNSCC. STUDY DESIGN: Randomized, prospective study in a hamster model. METHODS: Dysplastic lesions were induced in the cheek pouches of 48 hamsters by painting with topical 9,10-dimethl-1,2-benzanthrancene (DMBA). The hamsters were randomly divided into four treatment groups: 1) control (no treatment); 2) PDL irradiation only; 3) 5.0 mg RA (all-trans retinoid, 5.0 mg/kg per day, intraperitoneally [IP]); and (4) PDL + 0.5 mg RA (0.5 mg/kg per day, IP). The PDL irradiation was conducted at day 0 and 15, whereas the RA treatment was continued for 27 days. Tumor burden was measured over time. RESULTS: The lesions in all of three treatment groups grow more slowly than the untreated controls. The combination treatment of PDL and RA had the greatest inhibitory effect on tumors. CONCLUSION: This study suggests that combination treatment of PDL and low-dose RA is more effective than high-dose RA alone in the chemoprevention of HNSCC in a hamster cheek-pouch model, so that it should allow greatly improved tolerance of this regimen.     

Laparoscopic nephrectomy for unilateral multicystic dysplastic kidney in children

The contemporary management of children with unilateral multicystic dysplastic kidney remains controversial. With the potential risks of hypertension, infection, and malignant transformation of the dysplastic kidney, conservative management necessitates long-term review with frequent ultrasound scans, urine analyses, and blood pressure checks. Operative management has traditionally used open nephrectomy with its associated patient morbidity. The introduction of laparoscopic procedures has allowed the development of techniques that reduce patient morbidity, hospital stay, and analgesia requirement. This article reports a series of 13 children who underwent elective laparoscopic nephrectomy for unilateral multicystic dysplastic kidney and discusses the advantages this procedure has to offer for their management. The results for the initial seven patients in this series were presented to the British Association of Pediatric Endoscopic Surgeons Annual Meeting at St. Hilda’s College, Oxford, September 2002.     

Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: Report of the ISPOR Task Force for Translation and Cultural Adaptation

In 1999, ISPOR formed the Quality of Life Special Interest group (QoL-SIG)--Translation and Cultural Adaptation group (TCA group) to stimulate discussion on and create guidelines and standards for the translation and cultural adaptation of patient-reported outcome (PRO) measures. After identifying a general lack of consistency in current methods and published guidelines, the TCA group saw a need to develop a holistic perspective that synthesized the full spectrum of published methods. This process resulted in the development of Translation and Cultural Adaptation of Patient Reported Outcomes Measures--Principles of Good Practice (PGP), a report on current methods, and an appraisal of their strengths and weaknesses. The TCA Group undertook a review of evidence from current practice, a review of the literature and existing guidelines, and consideration of the issues facing the pharmaceutical industry, regulators, and the broader outcomes research community. Each approach to translation and cultural adaptation was considered systematically in terms of rationale, components, key actors, and the potential benefits and risks associated with each approach and step. The results of this review were subjected to discussion and challenge within the TCA group, as well as consultation with the outcomes research community at large. Through this review, a consensus emerged on a broad approach, along with a detailed critique of the strengths and weaknesses of the differing methodologies. The results of this review are set out as "Translation and Cultural Adaptation of Patient Reported Outcomes Measures--Principles of Good Practice" and are reported in this document.     

Influenza vaccine uptake and distribution in England and Wales using data from the General Practice Research Database, 1989/90-2003/04

BACKGROUND: Routinely collected data from patients registered with general practices participating in the General Practice Research Database (GPRD) were used to analyse influenza vaccine uptake and distribution in England and Wales between 1989/90 and 1996/97. Major changes to influenza immunization policy were introduced in 1998 and 2000 when immunization of the elderly became age related rather than risk related. This new study examines trends in vaccine uptake for high- and low-risk patients and the impact of the policy changes on uptake in the elderly. METHODS: Between 0.5 and 2.7 million patients registered with practices participating in the GPRD from 1989 to 2004 were included. Data were examined by age group, medical risk group and evidence of vaccination per study year. RESULTS: Vaccine uptake among high-risk persons aged 65 or more increased from 36.7 per cent in 1989/90 to 72.1 per cent in 2003/04. For the same period, uptake rates for high-risk persons under 65 years increased from 10.8 to 24.3 per cent. For those at high risk, uptake by females was higher in all age groups up to 65 years. Of those that were vaccinated, a higher proportion of the 65 and over were vaccinated in October each year compared with the high risk under 65 (p < 0.001). CONCLUSIONS: Coverage among high-risk patients in younger age groups continues to fall well below satisfactory levels, especially among the youngest groups. Government policy should now focus on ways to improve uptake in these patients.     

Elective laparoscopic appendicectomy for chronic right iliac fossa pain in children

AIM: To determine whether elective laparoscopic appendicectomy is justified for chronic right iliac fossa (RIF) pain of undetermined origin. METHODS: A retrospective audit of all laparoscopic appendicectomies between January 1997 and August 2003 was performed. The expanded medical audit system (EMAS) and a Microsoft Access database of operative records were used to identify patients with chronic RIF pain subjected to elective appendicectomy. Case notes were retrieved and analysed for patient profile, duration of symptoms including clinic visits and admissions, operative findings, histological analysis, and postoperative performance. A correlation between histological findings and final outcome was investigated. RESULTS: Ninety-eight patients underwent laparoscopic appendicectomy during the period of the study. A total of 11 cases with chronic RIF pain were identified. Nine were female and 2 male. Age ranged from 9 to 14 years with a mean of 11.9 years. The number of clinic visits and admissions for chronic RIF pain ranged from 2 to 8, with a mean of 4. Duration of symptoms ranged from 1 to 36 months, with a mean of 12.1 months. Detailed history, clinical examination, and serological and radiological investigations failed to reveal the cause of the pain in all cases. Patients were followed up in postoperative clinics for between 1 and 72 months, with a mean of 16.1 months. Histology of resected appendices showed acute inflammation (3 cases), fecoliths (2 cases), lymphoid hyperplasia (LH) (1 case), LH and a foreign body reaction (1 case), LH and mucosal hyperplasia (1 case), and Enterobius vermicularis parasites in 1 case. The appendix was normal in 2 cases. Eight patients had complete resolution of RIP pain. Seven of these had pathology within the appendix and 1 was histologically normal. Two patients with resolved RIF pain, but with pain elsewhere, had lymphoid hyperplasia noted within the appendix. One patient with persistent pain 6 years postoperatively had a normal appendix. CONCLUSION: This study demonstrates that a significant number of patients with chronic RIF pain have pathology within the appendix. The majority of these cases will benefit from elective appendicectomy. It is critical however that all other possible causes of pain in the RIF are excluded. Laparoscopy is an integral part of the diagnosis and management of this particularly difficult group of patients.