Biomedical subjects

Susan Alexander

Publications and source records attributed to Susan Alexander.

8 recordsLinked to original sources

PubMed2006

A biomechanical comparison of single and double-row fixation in arthroscopic rotator cuff repair.

BACKGROUND: The optimal method for arthroscopic rotator cuff repair is not yet known. The hypothesis of the present study was that a double-row repair would demonstrate superior static and cyclic mechanical behavior when compared with a single-row repair. The specific aims were to measure gap formation at the bone-tendon interface under static creep loading and the ultimate strength and mode of failure of both methods of repair under cyclic loading. METHODS: A standardized tear of the supraspinatus tendon was created in sixteen fresh cadaveric shoulders. Arthroscopic rotator cuff repairs were performed with use of either a double-row technique (eight specimens) or a single-row technique (eight specimens) with nonabsorbable sutures that were double-loaded on a titanium suture anchor. The repairs were loaded statically for one hour, and the gap formation was measured. Cyclic loading to failure was then performed. RESULTS: Gap formation during static loading was significantly greater in the single-row group than in the double-row group (mean and standard deviation, 5.0 +/- 1.2 mm compared with 3.8 +/- 1.4 mm; p < 0.05). Under cyclic loading, the double-row repairs failed at a mean of 320 +/- 96.9 N whereas the single-row repairs failed at a mean of 224 +/- 147.9 N (p = 0.058). Three single-row repairs and three double-row repairs failed as a result of suture cut-through. Four single-row repairs and one double-row repair failed as a result of anchor or suture failure. The remaining five repairs did not fail, and a midsubstance tear of the tendon occurred. CONCLUSIONS: Although more technically demanding, the double-row technique demonstrates superior resistance to gap formation under static loading as compared with the single-row technique. CLINICAL RELEVANCE: A double-row reconstruction of the supraspinatus tendon insertion may provide a more reliable construct than a single-row repair and could be used as an alternative to open reconstruction for the treatment of isolated tears.

Arthroscopy↗

PubMed2005

A national survey of laboratory animal workers concerning occupational risks for zoonotic diseases.

In this cross-sectional survey of laboratory animal workers in the United States, 23 of 1367 persons reported 28 cases of infection with zoonotic agents from research animals at their workplace during the past 5 years, with six persons indicating that their infections were medically confirmed. Based on these data, the annualized incidence rate for work-related transmission of zoonotic agents from laboratory animals was 45 cases per 10,000 worker-years at risk (95% confidence interval, 30 to 65 cases), approximating the rate for nonfatal occupational illnesses in the agricultural production-livestock industry and for those employed in the health services during 2002. Logistic regression analysis found various characteristics of persons and their employers that were significantly associated with the likelihood of having been medically evaluated for exposure to a zoonotic agent from laboratory animals. Most (95.595% +/- 1.1%) persons working with laboratory animals or their tissues indicated that they knew whom to talk to at their institution for medical evaluation and care should they be concerned about the possibility of an occupationally acquired zoonotic disease in future. However, occupational illnesses and exposures among laboratory animal workers was underreported, as 10 of the 28 (36%) alleged zoonotic disease cases were not communicated to the employee's supervisor. Lack of concern about the potential significance to their health and the perception of punitive consequences to the employee were some of the reasons cited for underreporting, an issue which must be vigorously addressed in the interests of continuing progress toward zoonotic disease prevention in this field.

Animals↗

PubMed2004

Proteomic analysis of articular cartilage shows increased type II collagen synthesis in osteoarthritis and expression of inhibin betaA (activin A), a regulatory molecule for chondrocytes.

We show that proteomic analysis can be applied to study cartilage pathophysiology. Proteins secreted by articular cartilage were analyzed by two-dimensional SDS-PAGE and mass spectrometry. Cartilage explants were cultured in medium containing [35S]methionine/cysteine to radiolabel newly synthesized proteins. To resolve the cartilage proteins by two-dimensional electrophoresis, it was necessary to remove the proteoglycan aggrecan by precipitation with cetylpyridinium chloride. 50-100 radiolabeled protein spots were detected on two-dimensional gels of human cartilage cultures. Of 170 silver-stained proteins identified, 19 were radiolabeled, representing newly synthesized gene products. Most of these were known cartilage constituents. Several nonradiolabeled cartilage proteins were also detected. The secreted protein pattern of explants from 12 osteoarthritic joints (knee, hip, and shoulder) and 14 nonosteoarthritic adult joints were compared. The synthesis of type II collagen was strongly up-regulated in osteoarthritic cartilage. Normal adult cartilage synthesized little or no type II collagen in contrast to infant and juvenile cartilage. Potential regulatory molecules novel to cartilage were identified; pro-inhibin betaA and processed inhibin betaA (which dimerizes to activin A) were produced by all the osteoarthritic samples and half of the normals. Connective tissue growth factor and cytokine-like protein C17 (previously only identified as an mRNA) were also found. Activin induced the tissue inhibitor for metalloproteinases-1 in human chondrocytes. Its expression was induced in isolated chondrocytes by growth factors or interleukin-1. We conclude that type II collagen synthesis in articular cartilage is down-regulated at skeletal maturity and reactivated in osteoarthritis in attempted repair and that activin A may be an anabolic factor in cartilage.

Activins↗

PubMed2004

Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose-response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose-response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Animals↗

PubMed2004

The unstable shoulder.

Not all unstable shoulders are the same, and careful patient selection ensures proper treatment. Improved understanding of the mechanisms of stability, advances in imaging and arthroscopic technology mean that repeated visits to the emergency department with a painful dislocated shoulder should be a thing of the past.

Emergency Treatment↗

PubMed2003

Wildfire effects on hiking and biking demand in New Mexico: a travel cost study.

We use a travel cost model to test the effects of wild and prescribed fire on visitation by hikers and mountain bikers in New Mexico. Our results indicate that net benefits for mountain bikers is $150 per trip and that they take an average of 6.2 trips per year. Hikers take 2.8 trips per year with individual net benefits per trip of $130. Both hikers' and mountain bikers' demand functions react adversely to prescribed burning. Net benefits for both groups fall as areas recover from prescribed burns. Because both visitation and annual recreation benefits decrease to these two types of visitors, this gives rise to multiple use costs associated with prescribed burning. With respect to wildfire, hikers and mountain bikers both exhibit decreased visitation as areas recover from wildfires, however, only hikers indicate an increase in per trip net benefits. Bikers' demand effectively drops to zero. These results differ from previous findings in the literature and have implications for efficient implementation of the National Fire Plan and whether prescribed burning is a cost effective tool for multiple use management of National Forests. Specifically, that fire and recreation managers cannot expect recreation users to react similarly to fire across recreation activities, or different geographic regions. What is cost effective in one region may not be so in another.

Bicycling↗

PubMed2002

Tissue inhibitor of metalloproteinase-3 is associated with neuronal death in reperfusion injury.

Programmed cell death occurs in ischemia when cell surface death receptors (DRs) are stimulated by death-inducing ligands (DILs). Matrix metalloproteinases are extracellular matrix-degrading enzymes involved in the shedding of DRs and DILs from the cell surface. Tissue inhibitor of metalloproteinase-3 (TIMP-3), which is bound to the extracellular matrix, has been shown to promote apoptosis in cancer cell lines by inhibiting cell surface sheddases. Since apoptosis is an important mechanism of cell death in ischemia, the authors hypothesized that TIMP-3 would be expressed in ischemic neurons that are undergoing programmed cell death. Spontaneously hypertensive rats had a 90-minute middle cerebral artery occlusion with reperfusion. Transcription of TIMP-3 mRNA was measured by quantitative reverse transcription-polymerase chain reaction at 2, 6, 24 and 48 hours after reperfusion. Western blots were used to measure TIMP-3 protein expression. Spatial distribution and production of TIMP-3 was studied by immunohistochemistry at 3, 24, and 48 hours, 5 days, and 3 weeks. DNA fragmentation in cells dying by necrosis and apoptosis was identified with terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL). After 2 hours of reperfusion, TIMP-3 mRNA increased significantly in both ischemic and nonischemic hemispheres. Western blot analysis confirmed the identity of the TIMP-3, which appeared to be increased on the ischemic side. After 3 hours of reperfusion, TIMP-3 immunostaining was increased in neurons on the ischemic side, and by 24 hours the majority of the ischemic neurons were TIMP-3-positive. Dual-fluorescence staining for TUNEL and TIMP-3 showed that they were coexpressed in many neurons. The results suggest that ischemic neurons express TIMP-3, which may be inhibiting sheddases. The authors propose that TIMP-3 facilitates cell death in ischemic neurons. Further studies are needed to identify the sheddases inhibited by the TIMP-3, and on the effect of inhibition of matrix metalloproteinases on cell death mechanisms.

Animals↗

PubMedDate not supplied

Clinicopathological features in 102 cases of Hirschsprung disease.

BACKGROUND: Hirschsprung disease [HD] is a predominantly childhood disorder of intestinal motility with a multifactorial and polygenic etiology. The objective of this study was to document the clinical and pathological features of HD in Kuwait, which has an estimated consanguinity rate of 54%. METHODS: We analyzed all rectal and colonic biopsies (n=268) for suspected HD identified from the records in the Pathology Department of Al-Sabah Hospital for the period between 1994 and 2004. RESULTS: One hundred and two patients (87 males and 15 females) had histologically confirmed HD. Fifty-eight (57%) were neonates (<1 month of age), while 21% were more than 4 months old. The diagnosis was based on open biopsy in 11 cases and rectal biopsies in 91 cases. Nine patients with open biopsies presented as intestinal obstruction, necrotizing enterocolitis, or perforation. The extent of the disease was unknown in 13 patients. There were 67 males and 3 females with short segment HD. Nine had long segment, two ultra-short segment and eight total colonic aganglionosis (TCA). Five TCA cases involved the small intestine. A skip area was observed in two cases. Six patients had other anomalies. A positive family history for HD was established in three patients. Two of these were male siblings from a consanguineous marriage and had Waardenburg syndrome. CONCLUSION: This study has highlighted an exceptionally strong male predominance of short segment and a relatively high frequency (5.6%) of small intestinal involvement in HD in Kuwait. These data call for a more detailed epidemiological study with special emphasis on genetics.

Adolescent↗