Development and evaluation of a multimedia resource pack for oral health training of medical and nursing staff.

A resource pack has been devised for training medical and nursing staff and other carers in order that they may recognize oral disease and carry out routine oral care and treat common oral disorders. The custom-designed folding pack contains a videotape, a CD-ROM disc, and an A5-sized spiral-bound booklet, together with wall posters and a list of useful addresses. One hundred of the packs were distributed across Scotland to medical, nursing, and dental staff involved in postgraduate medical and nursing education. The packs were independently evaluated by an external organization through a questionnaire and also by telephone interviews. The pack received very positive responses, and 35% of the respondents reported making changes to their current practice. A long-term measure of success, beyond the scope of this paper, will depend on the measurement of improved quality of oral health care of the patients in those institutions where the pack has been used in training.

Hard tissue ridge augmentation using a resorbable membrane and a particulate graft without complete flap closure.

Twelve patients with isolated alveolar ridge defects bordered by teeth on each side were treated and followed for 12 months. The treatment involved use of a resorbable membrane and a particulate graft without complete flap closure. Measurements taken at 12 months showed a significant mean osseous gain of 3.27 +/- 3.73 mm in mid-defect ridge width and an increase in height of 1.90 +/- 2.50 mm.

Heparin-binding epidermal growth factor-like growth factor is expressed in the adhesive lesions of experimental focal glomerular sclerosis.

BACKGROUND: In this study, we attempted to determine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) was up-regulated in two chronic models of proteinuria. METHODS: Chronic passive Heymann nephritis (PHN) and puromycin aminonucleoside (PAN) models were induced in Sprague-Dawley rats. HB-EGF expression was studied by Northern blotting, in situ hybridization, and immunohistochemistry. RESULTS: The chronic PAN model was associated with the development of glomerular lesions of focal glomerular sclerosis (FGS), severe interstitial fibrosis, and renal failure. Lesions of FGS were seen in approximately 80% of glomeruli at all time points, with a slight increase in the number of glomeruli showing extensive adhesion between 40 and 90 days. Northern blots of whole kidney tissue showed a 3- to 5.8-fold increased expression of HB-EGF mRNA in the chronic PAN group. Increased mRNA and protein were localized by in situ hybridization and immunohistochemistry to tubules, glomerular epithelial cells (GECs), and cells of Bowman's capsule. HB-EGF mRNA and protein were strongly expressed by epithelial cells involved in the formation of the lesions of FGS. By contrast, in chronic PHN, there was a small increase in HB-EGF, and the extensive lesions of FGS did not develop despite continued, heavy proteinuria. CONCLUSIONS: These data suggest that HB-EGF may contribute to formation of the lesions of FGS, perhaps through stimulation of abortive mitogenesis in GECs or an adhesive interaction between transmembrane HB-EGF and the exposed glomerular basement membrane.

Cutaneous necrosis from calcific uremic arteriolopathy.

Calcific uremic arteriolopathy (calciphylaxis) is an uncommon complication of chronic renal failure that is associated with high morbidity and mortality. We report 16 patients (13 female) who presented between 1985 and 1996. All patients developed painful livido reticularis that progressed to cutaneous necrosis and ulceration (11 cases on the proximal extremities and five cases on the distal extremities). Two patients with predominately distal leg disease survived; the cause of death in the other 14 patients was sepsis (six patients), withdrawal from dialysis (three), cardiac arrest (three), and gastrointestinal hemorrhage (two). Mesenteric ischemia from intestinal vascular calcification occurred in two cases. Clinical factors identified included the use of warfarin therapy in seven cases and significant weight loss (>10% body weight) in seven cases in the 6 months preceding the development of calcific uremic arteriolopathy. Skin pathology was studied in 12 cases, with all showing calcific panniculitis and small vessel calcification. Electron microscopic spectral analysis of the mineral content of the calcific lesions in the subcutaneous tissue showed only calcium and phosphorous. In two cases, substitution of low molecular weight heparin for warfarin therapy resulted in clinical improvement. Current theories of pathogenesis and treatment are reviewed. This study confirms the high morbidity and mortality of calcific uremic arteriolopathy producing ischemic tissue necrosis while drawing attention to significant weight loss and warfarin therapy as risk factors for the development of ischemic tissue necrosis. Hyperbaric oxygen therapy warrants further study.

Heparin-binding EGF-like growth factor mRNA is upregulated in the peri-infarct region of the remnant kidney model: in vitro evidence suggests a regulatory role in myofibroblast transformation.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent fibroblast and epithelial cell mitogen that may be important in wound healing. The aim of this study was to determine its distribution and possible function in segmental renal infarction. At day 1 postinfarction, in situ hybridization showed that HB-EGF mRNA was markedly increased by tubular epithelial cells bordering the infarcted zone. At day 3, typical myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA) were present in large numbers at the peri-ischemic border and, over succeeding days, were also seen within the infarcted area. Some of these cells expressed HB-EGF mRNA by in situ hybridization suggesting possible autocrine stimulation. Endothelial cells appeared to be more resistant to ischemia than tubules because some capillaries at the periphery of the infarct, surrounded by infarcted tubules, also expressed HB-EGF mRNA. The staining intensity of HB-EGF mRNA in individual tubules and endothelial cells was maximal at day 5 after infarction, although Northern blots of tissue from the peri-infarct area only showed significantly increased expression of HB-EGF mRNA at days 1 and 3, perhaps reflecting a smaller area of greater intensity of expression at day 5. Because tubular cells expressing high levels of HB-EGF mRNA were directly apposed to myofibroblasts, an attempt was made to determine whether HB-EGF contributed to upregulation of alpha-SMA by human fibroblasts. Although stimulation of the fibroblast cell line MRC-5 with transforming growth factor-beta1 (TGF-beta1) increased alpha-SMA, HB-EGF reduced expression. HB-EGF also strongly inhibited the increased expression of alpha-SMA due to TGF-beta1. Because HB-EGF is a potent fibroblast mitogen and TGF-beta is usually antiproliferative, this study suggests that HB-EGF may contribute to a local balance between fibroblast proliferation and differentiation into myofibroblasts during scarring.

Heparin-binding epidermal growth factor-like growth factor in experimental models of membranous and minimal change nephropathy.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently described member of the epidermal growth factor (EGF) family. It binds to heparan sulfate proteoglycans via a cationic domain and is a potent mitogen for epithelial cells, fibroblasts and vascular smooth muscle cells. In the present study we have attempted to identify changes in quantity and distribution of HB-EGF in two models of acute glomerular epithelial cell injury, using Western blotting, immunohistochemistry and in situ hybridization. Prior to disease induction, Western blots showed some expression of HB-EGF protein within glomeruli. Within the first three days in the acute puromycin aminonucleoside (PAN) and passive Heymann nephritis (PHN) models, immunohistochemistry and in situ hybridization demonstrated an up-regulation of HB-EGF mRNA and protein in glomerular epithelial cells (GEC). In both cases, increased protein and mRNA was found prior to the onset of proteinuria and continued until day 21 post-induction, the last time point studied. Early in the course of the models, HB-EGF was localized to the cytoplasm of glomerular epithelial cells. At day 21, however, HB-EGF protein was distributed in a nodular pattern within GEC and along the glomerular basement membrane (GBM) in both models, suggesting that the secreted form might bind to the membrane. The increase in HB-EGF protein within glomeruli was confirmed by Western blots of glomerular membrane protein which, however, demonstrated a single 29 kDa species, consistent with the transmembrane form. These data are not consistent with binding of the secreted form of HB-EGF to the GBM. The transmembrane form of HB-EGF is able to signal in a juxtracrine fashion, so increased expression of HB-EGF mRNA and protein by GEC might contribute to the genesis of proteinuria through the initiation of abortive GEC mitogenesis.

Classical polyarteritis nodosa and microscopic polyarteritis with medium vessel involvement--a comparison of the clinical and laboratory features.

Microscopic polyarteritis may involve medium-sized and small blood vessels as well as arterioles, venules and capillaries. We have compared the clinical and laboratory features in patients with microscopic polyarteritis and medium vessel involvement, with the features found in patients with polyarteritis nodosa affecting medium vessels alone. In a 9-year period, 21 patients presented to our hospital with a form of polyarteritis. Seven had microscopic polyarteritis demonstrated histologically (6/7, 86%) and associated with dysmorphic urinary red cells (7/7, 100%), as well as medium vessel vasculitis demonstrated histologically (7/7) or by angiography (1/7, 14%). Five patients had polyarteritis nodosa with medium vessel vasculitis demonstrated histologically (3/5, 60%) or by angiography (2/5, 40%); and no evidence of a glomerular vasculitis on biopsy (2/7, 29%) or in the urinary sediment (0/7, 0%). The remaining 9 patients had microscopic polyarteritis but medium vessel involvement was not excluded by angiography. All patients with microscopic polyarteritis and medium vessel involvement had glomerular hematuria (> 100,000 glomerular RBC/ml), proteinuria > 0.5 g/24 hours), and an elevated serum creatinine (0.166 to 0.811 mmol/l). Other symptoms included fever (6/7, 86%), night sweats (5/7, 71%), gastrointestinal bleeding (4/7, 57%), proximal myopathy (3/7, 43%) and peripheral neuropathy (3/7, 43%). One patient (1/7, 14%) had hypertension. Anemia (6/7, 86%), a raised ESR (6/7, 86%), thrombocytosis (6/7, 86%), hypoalbuminemia (6/7, 86%) and abnormal liver function tests (6/7, 86%) were common. Two patients (29%) had an eosinophilia. All 5 individuals who were tested for ANCA were positive (2cANCA, 2pANCA and one pattern not described). In contrast, in patients with polyarteritis nodosa and medium vessel involvement alone, an elevated ESR was common (4/5, 80%) but fever (1/5, 20%), night sweats (0/5, 0%), proximal myopathy (1/5, 20%) and peripheral neuropathy (1/5, 20%) were seen infrequently; hypertension (1/5, 20%) and eosinophilia (1/5, 20%) were also uncommon; and ANCA were not demonstrated (0/3, 0%). Medium-sized vessel involvement is common in patients with microscopic polyarteristis, and these patients are more likely to have renal involvement and systemic symptoms, and be ANCA-positive, than patients with polyarteritis nodosa alone. Gastrointestinal symptoms are often seen in both groups.

Exercise intolerance in Kearns-Sayre syndrome.

Exercise intolerance is a common finding in mitochondrial diseases, including Kearns-Sayre syndrome (KSS), characterised by progressive external ophthalmoplegia, cardiac conduction defects and atypical pigmentary degeneration of the retina. Exercise studies were performed in a 32 year old woman with KSS who had received an atrio-ventricular sequential pacemaker because of continuing breathlessness, having presented with complete heart block requiring a fixed rate demand pacemaker 6 years earlier. Minute ventilation, oxygen consumption, and carbon dioxide production were measured at different workloads on 3 consecutive days by collecting expired air. Compared to controls, after exercise at a subanaerobic workload, heart rate and ventilation were exaggerated relative to both oxygen consumption and carbon dioxide production. The findings are consistent with the hypothesis that, in mitochondrial disorders, impaired oxidative phosphorylation leads to uncoupling of cardiac ouput and ventilation relative to muscle metabolic rate.

Polyarteritis nodosa and antiglomerular basement membrane disease without antineutrophil cytoplasm antibodies.

Antiglomerular basement membrane (GBM) antibodies have been described previously in patients with microscopic polyarteritis but not in patients with polyarteritis nodosa alone. Where anti-GBM antibodies occur in microscopic polyarteritis, antineutrophil cytoplasm antibodies (ANCA) are usually present. We describe here a patient with polyarteritis nodosa and anti-GBM antibodies in whom ANCA could not be demonstrated. A 72-year-old woman presented with abdominal pain, diarrhoea and acute renal failure. A renal biopsy showed crescentic glomerulonephritis and linear immunofluorescence of the GBM consistent with anti-GBM disease. In addition, there was evidence of large-and medium-sized vessel vasculitis on abdominal angiography, performed because of persisting abdominal pain. There was no small vessel vasculitis on histological examination of the renal biopsy and ANCA could not be demonstrated by indirect immunofluorescence or ELISA.