Clinical and molecular findings in IPEX syndrome.

IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X linked syndrome) is a rare disorder which usually results in death in early infancy or childhood. Clinical awareness remains the cornerstone of diagnosis, and provided that the diagnosis is entertained, mutation analysis for FOXP3 gene mutations can be confirmatory. Two new patients in whom IPEX was diagnosed retrospectively are reported.     

An alternative to aorto-uni-iliac EVAR and femoro-femoral crossover in a patient having an aorto-iliac aneurysm with an occluded external iliac artery.

INTRODUCTION: An endovascular procedure for excluding an aorto-iliac aneurysm whilst simultaneously preserving one internal iliac artery is described in a patient with complex iliac pathology. REPORT: The procedure involved the use of Advanta V12 covered stents to bridge the gap between the contralateral limb of the main body of a custom-made Zenith stent graft and the internal iliac artery on the side of an external iliac artery occlusion. DISCUSSION: Minimal modifications to the standard design of modular stent grafts make it possible to treat high risk patient with complex pathology with minimal morbidity.     

Four-Year Follow-up on Endovascular Radiofrequency Obliteration of Great Saphenous Reflux

BACKGROUND: Endovascular radiofrequency obliteration has been used since 1998 as an alternative to conventional vein stripping surgery for elimination of saphenous vein insufficiency. OBJECTIVE: To demonstrate the long-term efficacy of this treatment modality. METHODS: Data were prospectively collected in a multicenter ongoing registry. Only great saphenous vein above-knee treatments were included in this study. Eight hundred ninety patients (1,078 limbs) were treated prior to November 2003 at 32 centers. Clinical and duplex ultrasound follow-up was performed at 1 week, 6 months, and 1, 2, 3, and 4 years. RESULTS: Among 1,078 limbs treated, 858 were available for follow-up within 1 week, 446 at 6 months, 384 at 1 year, 210 at 2 years, 114 at 3 years, and 98 at 4 years. The vein occlusion rates were 91.0%, 88.8%, 86.2%, 84.2%, and 88.8%, respectively; the reflux-free rates were 91.0%, 89.3%, 86.2%, 86.0%, and 85.7%, respectively; and the varicose vein recurrence rates were 7.2%, 13.5%, 17.1%, 14.0%, and 21.4%, respectively, at each follow-up time point at 6 months, and 1, 2, 3, and 4 years. Patient symptom improvement persisted over 4 years. CONCLUSIONS: Endovascular temperature-controlled radiofrequency obliteration of saphenous vein reflux exhibits an enduring treatment efficacy clinically, anatomically, and hemodynamically up to 4 years following treatment.     

The computer as a diagnostic consultant, with emphasis on use of laboratory data

In this preliminary study concerning the applicability of expert computer systems, such as INTERNIST-I, to providing advice to clinical pathologists regarding patients' diagnoses and the pertinence of performing further laboratory tests, 32 complex cases, drawn from Case Records of the Massachusetts General Hospital, were analyzed diagnostically by computer, on the basis of clinical laboratory data only. Half (16 cases) were diagnosed correctly, but in 15 of the rest no diagnostic conclusion could be reached. However, no diagnostic errors were made. The study provides preliminary evidence that expert computer systems can be useful to clinical pathologists and clinical internists in guiding the laboratory workup of patients toward correct diagnosis.     

The Future Detection and Prevention of Institutional Abuse: Giving Children a Chance to Participate in Research

The involvement of children in research studies is historically fraught with difficulties. Experiments on children without their consent or knowledge have been carried out in the past and thus the need for stringent ethical control is undoubtedly necessary. However this paper argues that the need to protect children from unethical research has somehow become entwined in the web of secrecy that surrounds the very nature of child abuse. In the name of 'protection' are children in danger of not having their voice heard?

In the foreword to 'Listening to Children' (Alderson, 1995) Roger Singleton writes, 'much research is carried out on and about children, but seldom with children. Children themselves are often strangely silent'. This paper draws on recent literature on the institutional abuse of young people in residential care and the lack of voice that those abused in residential care have traditionally had, suggesting that their silence is not 'strange' but perhaps contrived.

This paper does not repeat the work of Alderson (1995) and make suggestions as to how research with children may best be carried out, but seeks to address the issues in relation to research with children who are in institutions.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Mentoring in inservice training for child care workers

A model for training the trainers of child care providers that employs Vygotsky's framework of the Zone of Proximal Development is described. This efficient training mechanism proposes mentoring relationships as a means to meet the developmental needs of experienced child care professionals and improve the quality of existing child care programs.The authors would like to thank Dr. Bille Thomas and the satellite resource center directors and staff members for their work on the project.     

Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs

In the presence of fixed basal levels of insulin, the route of intravenous glucose delivery (protal vs. peripheral) determines whether net hepatic glucose uptake (NHGU) occurs. Our aims were to determine if the route of intravenous glucose delivery also plays a role in regulating NHGU in the presence of hyperinsulinemia and to determine if length of fast (18 vs. 36 h) influences regulation of NHGU. Five conscious dogs fasted 18 h were given somatostatin and replacement insulin (245 +/- 34 microU.kg-1.min-1) and glucagon (0.65 ng.kg-1.min-1) infusions intraportally. After a 40-min control period, the insulin infusion rate was increased fourfold, and glucose was infused for 3 h. Glucose was given either through a peripheral vein or the portal vein for 90 min to double the glucose load reaching the liver. The order of infusions was randomized. NHGU was measured with the arterial - venous difference technique. Insulin and glucagon levels were 12 +/- 2, 35 +/- 6, and 36 +/- 5 microU/ml and 55 +/- 12, 61 +/- 13, and 59 +/- 7 pg/ml during the control, peripheral, and portal infusions, respectively. The glucose infusion rate, the load of glucose reaching the liver, and the arterial-portal plasma glucose gradient were 0, 9.58 +/- 2.28, and 10.44 +/- 2.94 mg.kg-1.min-1; 29.4 +/- 3.6, 56.8 +/- 3.4, and 56.8 +/- 2.8 mg.kg-1.min-1; and 2 +/- 1, 5 +/- 1, and -51 +/- 15 mg/dl during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)