Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities.

An unusual, elongated, refractile cell morphology was observed in keratinocytes cultured from three patients with non-lethalis forms of junctional epidermolysis bullosa (JEB). To determine whether these changes might be related to altered cell adhesion, keratinocyte strains established from one patient were examined for adhesive, structural, and functional characteristics. JEB keratinocytes expressed keratin tonofilaments, as determined by staining with AE1 monoclonal antibodies and direct observation of tonofilaments by electron microscopy. JEB keratinocytes showed diminished cell-substratum adhesions, judged by interference reflection microscopy. Areas of diminished cell-substratum adhesion corresponded to F-actin-rich cell adhesions (focal adhesions) and not to cellular areas that abundantly express hemidesmosomal antigens. Analysis of cell-substratum adhesion by electron microscopy revealed extensive areas of cell-substratum separation in JEB keratinocytes that were not present in normal keratinocytes maintained in serum-free medium. Normal keratinocytes displayed numerous regions of focal contact between the ventral plasma membrane and the culture substratum, but these structures were not seen in JEB keratinocytes. Bundled actin filaments (stress fibers) were greatly diminished in expected regions of cell-substratum adhesion in JEB keratinocytes and, instead, displayed disorganized individual filaments. The growth rate of JEB keratinocytes was quite slow in culture, with a population doubling time of 2.7 d versus 1.5 d for normal keratinocytes under identical conditions. JEB keratinocytes also displayed a reduced ability to aggregate into colonies upon exposure to medium with increased extracellular calcium. JEB keratinocytes thus display adhesive, structural, and functional abnormalities that suggest this cell type may be central to the pathogenesis of junctional epidermolysis bullosa. Study of affected keratinocytes could be important to characterize associated molecular pathologies.     

Warping of cross sections in the torsion of long bones with internal fracture fixation plates

Torsion of noncircular beams results in warping of each cross section. When noncircular cross sections are constrained to remain plane, the resulting shear stress distribution is different from what Saint Venant torsion (with warping) would predict. This has practical implications to the stress analysis of plated long bones subjected to torsional loadings. Analyses in which warping is not allowed predict incorrect stress fields in the plate and bone and overpredict the amount of stress shielding associated with fracture plate fixation.     

Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily.

     

Meta-analysis of the effects of educational and psychosocial interventions on management of diabetes mellitus

A meta-analysis of the literature of controlled studies of educational and psychosocial interventions in the treatment of diabetes mellitus yielded 93 studies of 7451 patients testing the effects of eight intervention types: (1) didactic education, (2) enhanced education, (3) diet instruction, (4) exercise instruction, (5) self-monitoring instruction, (6) social learning/behavior modification, (7) counseling, and (8) relaxation training. An overall mean effect size (ES) of +0.51 +/- 0.11 was found moderate but significant (P less than 0.05) improvements for all intervention subjects. Physical outcome and knowledge gain were most affected, followed by psychological status and compliance. Diet instruction and social learning interventions showed the strongest (ES = +0.68 +/- 0.58 and ES = +0.57 +/- 0.42, respectively) and relaxation training the weakest (ES = +0.30 +/- 0.74) effects. Associations between study and sample characteristics and mean ES values were explored with type of setting and methodological weaknesses such as single group design and non-random assignment achieving statistical significance. Neither intervention type, number of visits, sex, age, nor type of diabetes were significantly correlated with mean ES values. Implications of these findings for clinical treatment and future research are discussed.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Computer predictions of bone remodeling around porous-coated implants

Computer simulations of bone remodeling in response to mechanical stresses can be used to understand normal growth and development of the skeleton or to predict the remodeling of bone in response to prosthetic devices. Using a previously derived bone maintenance theory, a technique for computing bone density distributions was applied to the proximal femur and tibia using two-dimensional, multiple-loading finite element models. The models initially represented solid, homogeneous structures. Using an iterative bone remodeling technique that relates bone apparent density to loading history, the internal distributions of apparent density and elastic modulus for the normal bones were predicted. The finite element models were then modified to represent bones in which porous-coated femoral surface replacements and tibial tray components had been implanted. The same iterative remodeling method was then applied to predict the distribution of bone around these components. The predicted bone density distributions for the natural femur and tibia agree with previously documented normal bone morphology. The predicted bone density distributions around various implanted prostheses were characteristic of the component under investigation and were consistent with clinical and experimental findings of other investigators. In the femoral head, stress shielding occurred underneath the metal surface replacement cup, resulting in lower densities in the femoral head. The addition of a central femoral cup fixation peg caused bone hypertrophy around the peg. In the tibia, the stress concentrations around the pegs also resulted in denser bone, with a concomitant decrease in bone density at more peripheral locations underneath the prosthetic tray. This remodeling technique has the potential to be an important tool in predicting the possible remodeling consequences of new implant design features.     

颈内动脉接近完全闭塞时的处理

目的由于卒中风险随着狭窄严重程度的增加而升高，因此认为颈内动脉（ICA）接近闭塞患者的卒中风险很高。在现有的随机试验中，还没有专门针对这种情况进行探讨，因此其处理尚存在争汶。方法：对相关文献进行系统评价。结果：对ICA接近闭塞患者的处理还存在争议：一些学者支持进行干预，而另一些学者则认为存在风险或没有益处而反对进行干预。在ICA接近闭塞的有症状患者中进行一项比较外科治疗与最佳内科治疗的多中心前瞻性随机试验似乎非常困难，因为这类研究需要大量的患者。尽管如此，基于目前的证据，似乎很难拒绝手术治疗。结论：由于目前对ICA接近闭塞患者的最佳处理方案仍存在着争议，因此需要前瞻性观察性研究以证实其在有症状和无症状人群中的患病率以及相关的卒中风险。基于目前的证据，大多数医疗中心选择手术治疗，但它相对干内科治疗的特粱尚右待证章．