IgA-epidermolysis bullosa acquisita in a child resulting in blindness

Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen, the major component of anchoring fibrils. The classical phenotype of EBA is a non-inflammatory, mechanobullous disease resembling the dystrophic forms of inherited epidermolysis bullosa. Mucous membrane involvement is frequent but usually mild. We report a 1-year-old girl suffering from IgA-EBA, who presented with an initial eruption of disseminated urticarial lesions and tense blisters of the skin but subsequently developed severe oral and ocular lesions reminiscent of cicatricial pemphigoid. Direct immunofluorescence of the skin and buccal mucosa revealed linear IgA and C3 at the basement membrane zone (BMZ). IgA anti-BMZ autoantibodies stained the dermal side of salt-split skin by indirect immunofluorescence and recognized a dermal protein of 290 kDa co-migrating with type VII collagen by immunoblotting. Direct and indirect immunoelectron microscopy revealed IgA deposits overlying the anchoring fibrils. The ocular involvement led to total blindness in spite of intense treatment. This case of childhood IgA-EBA is particularly striking because of the cicatricial pemphigoid phenotype with severe ocular involvement which resulted in blindness. It reinforces the necessity to use modern immunological methods to classify autoimmune bullous diseases in order to allow early and appropriate treatment.     

Three-dimensional fetal echocardiography: gated versus nongated techniques.

The purpose of this study was to compare gated with nongated three-dimensional fetal echocardiography in terms of the ability to demonstrate fetal cardiac anatomy. We examined nine fetuses in utero using conventional two-dimensional sonographic imaging equipment, an electromagnetic position sensor, and a computer-graphics workstation. Free-hand sweeps were performed through the fetal heart and great vessels in either transverse or sagittal orientations with respect to the fetal heart. Seven transverse and five sagittal sweeps were selected for reconstruction and analysis. Cardiac gating was performed by using a temporal Fourier transform to determine the fundamental frequency of cardiac motion. Two-dimensional data from each sweep were reprojected to a series of volume data sets. Each series was then condensed to a single volume, so that each two-dimensional sweep could be compared with its respective gated and nongated volume data sets. The two-dimensional data were reviewed utilizing a display with forward and backward cineloop capability. The gated and nongated volume data sets were displayed interactively as a series of three orthogonal planes, with the ability of the observer to control the location of each image plane within the volume. The gated data were animated with variable display frame rates. Conventional two-dimensional imaging provided a fairly complete evaluation of the fetal heart when scanning included the four-chamber view with a sweep across the outflow tracts. Nongated three-dimensional fetal echocardiography allowed visualization of some structures and views not demonstrated with two-dimensional ultrasonography. Gated three-dimensional fetal echocardiography provided significantly better visualization and comprehension of cardiac anatomy than nongated three-dimensional fetal echocardiography. The superiority of gated over nongated three-dimensional fetal echocardiography appears to come from both improved image quality and the anatomic clues that derive from the ability to view cardiac motion.     

Cochrane Lecture 1997. What evidence do we need for evidence based medicine?

As presently understood, evidence based medicine aims to advance practice from its traditional unverifiable mix of art and science to rational use of measurable inputs and outputs. In practice, however, its advocates accept uncritically a desocialised definition of science, assume that major clinical decisions are taken at the level of secondary specialist rather than primary generalist care, and ignore the multiple nature of most clinical problems, as well as the complexity of social problems within which clinical problems arise and have to be solved. These reductionist assumptions derive from the use of evidence based medicine as a tool for managed care in a transactional model for consultations. If these assumptions persist, they will strengthen reification of disease and promote the episodic output of process regardless of health outcome. We need to work within a different paradigm based on development of patients as co-producers rather than consumers, promoting continuing output of health gain through shared decisions using all relevant evidence, within a broader, socialised definition of science. Adoption of this model would require a major social and cultural shift for health professionals. This shift has already begun, promoted by changes in public attitudes to professional authority, changes in the relation of professionals to managers, and pressures for improved effectiveness and efficiency which, contrary to received wisdom, seem more likely to endorse cooperative than transactional clinical production. Progress on these lines is resisted by rapidly growing and extremely powerful economic and political interests. Health professionals and strategists have yet to recognise and admit the existence of this choice.     

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus

Background : Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.
Aim : To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.
Methods : An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.
Results : The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.
Conclusion : In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Beurteilung der Häufigkeit chirotherapeutischer Leistungen

Ohne Zusammenfassung     

Malignant fibrous histiocytoma of the temporal bone with endocranial extension.

Cranial malignant fibrous histiocytomas are rare tumors. Most are hypervascular, destructive masses that are similar to other malignant lesions and to malignant fibrous histiocytomas found elsewhere in the body. We describe a myxoid malignant fibrous histiocytoma of the temporal bone, possibly of dural origin, with features that more closely resembled a meningioma at CT, MR imaging, and angiography.     

The Family System Test (FAST)

The impact of a cancer diagnosis upon a family has become a focus of clinical interest, but few scientific studies have been completed in this area. The objectives of this pilot study were twofold: first, to test the applicability of the Family System Test (FAST) in families (n=5) with a young adult member with cancer and secondly to evaluate patterns of interactions within these families. Results show that the FAST is applicable and useful to evaluate the different perceptions of hierarchy and cohesion - two essential variables - within these families. The great majority of family members represented their relationships as balanced (i.e., cohesive and moderately hierarchical). However, contrary to nonclinical families, fathers had a less positive view than mothers and patients: fathers more often perceived family and parenteral relations as unbalanced, and also more often perceived a reversal of hierarchy and a cross-generational coalition within the family. Implications for future research and clinical care are discussed.     

In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.