Detailed pathological changes of human lumbar facet joints L1–L5 in elderly individuals

Facet joints play an important role in intervertebral load transmission and are crucial for rotational kinematics. Clinically, the role of facet joints as a possible source of low back pain is seen as controversial and at present is not sufficiently investigated. In this study, human lumbar facet (zygapopyhysial) joints from donors with advanced age were analyzed macroscopically, for degenerative changes. The aim was to determine the extent and morphology of degenerative changes in these joints. Lumbar facet joints (L1–L5) of 32 donors were studied (mean age 80.1±11.2 years). Joint capsules were carefully removed and joint surfaces (5 zones) examined using magnifying glasses and probes. In the result, the majority of facet joints showed cartilage defects of varying extent. Defects were located mostly at the margins of the articular surface, the central zone being relatively well preserved. Defect localization was different between superior (most cartilage defects in superior zone) and inferior (most defects inferiorly) facets. Further, defects were more severe caudal (level of L5) and in older persons. Osteophytes were present in up to 30%, located mostly at the latero-dorsal enthesis of the joint capsule on the superior facet. In conclusion, most margins of the articular facets are subject to degenerative changes in the lumbar spine of elderly persons, the topographical pattern being different in superior and inferior facets. This observation can be explained by the segmental motion patterns during extension/flexion movements of the facets. Sometimes, due to the marginal extension, it is obvious that not all changes can be assessed by CT or MRI.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

A study of periapical lesions correlating the presence of a radiopaque lamina with histological findings.

OBJECTIVE: To compare the presence or absence of a radiopaque lamina of 60 human periapical lesions with the histological findings from a case study in dental practice. STUDY DESIGN: Paralleling radiographs were taken of 60 teeth with periapical radiolucencies. The periapical radiographs were scanned, and standardized images were evaluated on a computer screen for the presence or absence of a radiopaque lamina by 2 calibrated observers according to agreed criteria. The serially sectioned histological specimens were obtained from the extraction of 13 endodontically treated teeth and 27 nontreated teeth, as well as 20 post-treatment teeth with apical periodontitis removed during periapical surgical procedure; the specimens were classified according to agreed criteria. The findings of the 2 evaluations were compared. RESULTS: Out of 57 electronic images that could be interpreted, 10 lesions had a radiopaque lamina, but of these only 3 were histologically diagnosed as cysts, while 7 were granulomas or abscesses. Out of 47 lesions without a radiopaque lamina, 40 were histologically diagnosed as granulomas or abscesses, while 7 were cysts. CONCLUSIONS: The diagnosis of periapical lesions cannot be made on the basis of the presence or absence of a radiopaque lamina, but requires histological examination of serial sections.     

Velopharyngeal function during vocalization in infants.

OBJECTIVE: To determine the age at which infants achieve velopharyngeal closure during vocalization. DESIGN: Longitudinal with repeated measures. SETTING: Laboratory. PARTICIPANTS: Six healthy infants were studied monthly from ages 2 to 6 months while they interacted with a parent and an investigator. MAIN OUTCOME MEASURES: The presence or absence of velopharyngeal closure, as determined by sensing ram pressure at the anterior nares. RESULTS: The velopharynx was open for windups, whimpers, and laughs, and it was closed for cries, screams, and raspberries, regardless of age. The frequency with which the velopharynx closed during syllable utterances increased significantly with age. CONCLUSIONS: Velopharyngeal closure for speech-like utterance increases with age, but is not complete and is still undergoing development at 6 months of age. Velopharyngeal closure during infancy may be influenced by pressure demands of the utterance; however, support for this speculation is stronger for other types of utterances than it is for speech-like utterances. The method used in this study holds promise for evaluating infants with suspected velopharyngeal impairment.     

Fetal growth patterns in fetuses of women with pregestational diabetes mellitus.

OBJECTIVE: To assess the effect of glucose control on the rate of growth of fetuses in women with pregestational diabetes mellitus (Types 1 and 2). METHODS: All pregestational diabetic women booked at Mater Mothers' Hospital, Brisbane, Australia, between 1 January 1994 and 31 December 2002, were included. Pregnancies with congenital fetal anomalies, multiple pregnancies, and pregnancies terminated prior to 20 weeks' gestation were excluded. Dating scans were performed before 14 weeks' gestation and serial scans were performed at 18, 24, 28, 32 and 36 weeks. Fetal parameters, including biparietal diameter, femur length and abdominal circumference, were recorded. The daily growth rates for biparietal diameter, femur length, and fetal abdominal area were calculated and compared with those in a low-risk (non-diabetic) population. The growth rates in fetuses of women with satisfactory diabetic control (HbA1c < 6.5%) and unsatisfactory control (HbA1c > or = 6.5%) in the three trimesters were compared. RESULTS: A total of 174 diabetic pregnancies were included and a total of 997 ultrasound scans were performed. The growth rates for fetuses of mothers with diabetes mellitus were significantly higher than for those in the low-risk population. The z-scores for biparietal diameter, femur length, and fetal abdominal area were 0.18, 0.59 and 1.44, respectively. Fetuses of diabetic mothers with high HbA1c in the first trimester had significantly greater fetal abdominal area growth rate than those with normal HbA1c (fetal abdominal area z-score of 1.7 vs. 0.75, P = 0.009). Although the fetal abdominal area z-scores in fetuses of diabetic mothers with high HbA1c in the second or third trimesters were also higher than those with normal HbA1c levels, the differences did not reach statistical significance. Maternal obesity did not influence the fetal growth rate. CONCLUSION: The rate of growth of fetuses of diabetic mothers differs from that of the normal population. Growth acceleration persists until the late third trimester. Moreover, periconceptional glucose control appears to have a significant effect on accelerated growth of the fetal abdominal area.     

Real‐time RF pulse adjustment for B0 drift correction

Although the magnetic field of an MR scanner is very stable under little or no load, it can become less stable under heavy‐duty cycle conditions, such as in diffusion tensor imaging (DTI). Uncorrected, such field drifts lead to an apparent image shift along the phase‐encoding direction and decreasing effectiveness of fat saturation pulses. A method is presented to adjust the center frequency of all RF pulses and the receiver in real time during the acquisition. No data postprocessing or changes to the sequence timing are necessary. In vivo acquisitions were performed to assess the prolonged effectiveness of fat saturation. Field drifts of approximately 2.5 Hz/min were measured and corrected during DTI acquisitions at b‐values of up to 3000 s/mm². The effectiveness of fat saturation diminished over the duration of an 18‐min acquisition when the drift was left uncorrected. The proposed method corrects for apparent image shift and ensures continuously effective fat saturation over the duration of an acquisition. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.     

The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.