Mental status and fragile X expression in relation to FMR-1 gene mutation

The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat in the FMR-1 gene. Clinical expression is associated with a large expansion of the CGG repeat. The mutation in the FMR-1 gene and the cytogenetic expression of the fragile site at Xq27.3 have been studied in 52 fragile X male patients. The percentage of the cytogenetic expression of the fragile site at Xq27.3 positively correlates with the mean size of the full mutation in the FMR-1 gene (p < 0.0001) irrespective of the presence of additional premutation alleles. We noted a less frequent occurrence of additional premutation alleles in adult patients compared with juveniles, suggesting a continued mitotic instability in life. Additionally, the level of mental retardation has been ascertained in 35 patients using the Stanford-Binet or Terman-Merrill test of general intelligence. The presence of a full mutation in the FMR-1 gene seemed decisive for the occurrence of mental impairment in the patient. No correlation is observed between the degree of mental retardation and the size of the full mutation. The degree of mental retardation seemed not to be influenced by the presence of premutation alleles in part of the cells in addition to a full mutation. One patient is described with the 'Prader-Willi-like' subphenotype of the fragile X syndrome, showing a deletion in the FMR-1 gene in a part of his cells in addition to a full mutation.     

Porous-coated total hip replacement

Fifteen years of clinical experience with porous-coated prostheses demonstrated the durability of this type of fixation. This experience was documented by clinical follow-up study of the 393 cases treated by the senior author before 1985. Only six of these femoral components have been revised: three for loosening, two for stem breakage, and one for infection. Thus, the revision rate for the porous-coated stems was 1.5%. Porous-coated acetabular components were used in 227 of the arthroplasties. Five of these porous-coated cups have been revised: four for malposition leading to dislocation and one for late loosening secondary to osteolysis. Thus, the revision rate for these porous-coated acetabular components was 2.2%. Twenty bipolar and 146 cemented acetabular components were used in the remaining 166 cases treated before 1985. Eleven (7.5%) of the cemented acetabular components were revised. Revisions of the porous-coated components were rare in the first ten postoperative years. The clinical data were supplemented with analysis of postmortem specimens from 15 patients. Mechanical testing of the femoral specimens showed the relative micromotion at the porous surface to be exceptionally small (less than 40 microns). Seven of these postmortem retrievals involved cases with unilateral arthroplasties. In these cases, the contralateral normal femur also was removed, and a prosthesis identical to that in the in vivo implanted side was inserted to simulate the immediate postoperative condition. Dual-energy X-ray absorptiometry (DEXA) of the seven paired femora demonstrated that bone remodeling can be expected to produce a 5%-52% loss of periprosthetic bone mineral content, with the greatest loss occurring in the more osteoporotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells

We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself.     

Bond strength of adhesive resin to three nickel-chromium alloys with varying chromium content

This in vitro study evaluated the influence of chromium content on bond strength and durability between nickel-chromium alloys and an adhesive resin that contained 4-methacryloxyethyl trimellitate anhydride. Three nickel-chromium alloys with different chromium content, as well as pure chromium and pure nickel metals, were bonded and tested for shear strength. After repeated thermocycling, shear bond strength decrease was lower in alloys containing high chromium content. Pure chromium metal demonstrated a 15.2% decrease, whereas pure nickel metal demonstrated the greatest (53.7%) decrease. The results suggest that nickel-chromium alloys with higher chromium content are desirable for 4-methacryloxy-ethyl trimellitate anhydride resin-bonded restorations.     

Incidence and recognition of malnutrition in hospital

OBJECTIVES: To determine incidence of malnutrition among patients on admission to hospital, to monitor their changes in nutritional status during stay, and to determine awareness of nutrition in different clinical units. DESIGN: Prospective study of consecutive admissions. SETTING: Acute teaching hospital. SUBJECTS: 500 patients admitted to hospital: 100 each from general surgery, general medicine, respiratory medicine, orthopaedic surgery, and medicine for the elderly. MAIN OUTCOME MEASURES: Nutritional status of patients on admission and reassessment on discharge, review of case notes for information about nutritional status. RESULTS: On admission, 200 of the 500 patients were undernourished (body mass index less than 20) and 34% were overweight (body mass index > 25). The 112 patients reassessed on discharge had mean weight loss of 5.4%, with greatest weight loss in those initially most undernourished. But the 10 patients referred for nutritional support showed mean weight gain of 7.9%. Review of case notes revealed that, of the 200 undernourished patients, only 96 had any nutritional information documented. CONCLUSION: Malnutrition remains a largely unrecognised problem in hospital and highlights the need for education on clinical nutrition.     

Volume-activated chloride currents in pancreatic duct cells

OBJECTIVE: To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue. METHODS: Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads. RESULTS: Treatment with SLN resulted in a time- and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN: Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with high-frequency streaming potential measurements. CONCLUSION: Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.