Patterns and implications of lower extremity injuries in a community level I trauma center

This study examined specific types of lower extremity injuries, their treatment, and trends in length of stay (LOS) as seen in an academic community hospital. The authors' trauma registry was queried for lower extremity injuries requiring surgical intervention from 1992 to 2000. A total of 5567 patients were identified. A total of 574 patients with 857 injuries met the criteria. The only significant difference in injury severity score among various injury types was found between traumatic amputations and open fractures (P = 0.006). However, there was no statistical difference between these 2 groups with regard to LOS. Patients requiring 1 or 2 procedures had a significantly shorter LOS than those requiring 3 procedures (P = 0.002 and P = 0.021 respectively). In this population of patients, it was not the manner of initial reconstruction, but the number of reconstructive procedures required that had an impact on LOS. LOS reduction might be possible when patients with lower injury severity scores can be treated in a more efficient manner.     

Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice

Background/purpose

Anorectal malformations occur in 1 per 4,000 live births and represent a surgical challenge. Although critically important, the basic mechanisms of normal anorectal union are incompletely understood. Fgf10 signaling is known to serve a key role in mesenchymal/epithelial interactions in many organ systems including the gastrointestinal tract (GIT). The authors therefore hypothesized that Fgf10 signaling has a central role in normal anorectal development.

Methods

Fgf10 expression in wild-type (Wt) embryos was evaluated using whole-mount in situ hybridization. Wt and Fgf10^−/− embryos were harvested from timed pregnant mothers at E12.5 through E17.5 and were analyzed for anorectal phenotype.

Results

Wt development of union between anorectal structures is completed between E12.5 and E13.5 with luminal communication between distal rectal epithelium and anus. Fgf10 is discreetly expressed at E12.5 in the distal rectum. Fgf10^−/− mutants show failure of union of the rectum and anus at an early stage (E13.5) and near term (E17.5).

Conclusions

Fgf10 is expressed in the rectum at the time when anorectal continuity is established, indicating a role in normal anorectal development. Fgf10 invalidation (Fgf10^−/− mutant) results in a genetically reproducible anorectal malformation phenotype. Fgf10 function is critical for normal anorectal development.     

A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway

BACKGROUND: Intestinal atresia represents a significant surgically correctable cause of intestinal obstruction in neonates. Intestinal development proceeds as a tube-like structure with differentiation along its axis. As the intestine differentiates, the cecum develops at the transition from small to large intestine. Fgf10 is known to serve a key role in budding morphogenesis; however, little is known about its role in the development of this transitional structure. Here we evaluate the effect of Fgf10/Fgfr2b invalidation on the developing cecum. MATERIALS AND METHODS: Wild-type C57Bl/6, Fgf10(-/-), and Fgfr2b(-/-) embryos harvested from timed pregnant mothers were analyzed for cecal phenotype, Fgf10 expression, and differentiation of smooth muscle actin. RESULTS: Wt cecal development is first evident at E11.5. FGF10 is discreetly expressed in the area of the developing cecum at early stages of development. One hundred percent of Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with absence of epithelial and muscular layers. The development of neighboring anatomical structures such as the ileocecal valve is not affected by Fgf10/Fgfr2b invalidation. CONCLUSIONS: FGF10 expression is localized to the cecum early in the normal development of the cecum. Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with complete penetrance. Epithelial and muscular layers of the cecum are not present in the atretic cecum. The Fgf10(-/-) and Fgfr2b(-/-) mutants represent a genetically reproducible animal model of autosomal recessive intestinal atresia.     

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study

BACKGROUND: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database. METHODS: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD. LIMITATIONS: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable. CONCLUSIONS: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.     

Peripheral thyroid hormones and response to selective serotonin reuptake inhibitors

OBJECTIVE: To examine the relation between baseline measurements of thyroid function and response to selective serotonin reuptake inhibitors (SSRIs) and to consider the effect of these antidepressants on thyroid hormone levels. METHODS: Nineteen subjects with major depression, but without a history of thyroid treatment or lithium treatment, were treated openly with either sertraline or fluoxetine in a university- affiliated tertiary care hospital. Hamilton Depression Rating Scale (Ham-D) scores were measured before and after treatment. Clinical Global Impressions (CGI) scores were measured at study end. Thyroid data, consisting of values for thyroid-stimulating hormone (TSH), triiodothyronine (T(3), measured by radioimmunoassay [RIA]), thyroxine (T(4), measured by RIA) and free T(4), were collected before and after treatment. Complete thyroid data were available for 17 subjects. Data were collected during 1997-1999. RESULTS: Baseline TSH correlated strongly with response to treatment as measured by change in Ham-D scores (r = 0.64, p = 0.003). Low TSH values correlated with greater improvement in depressive symptoms. Thyroid hormone levels decreased with treatment, but these decreases did not correlate with clinical improvement. CONCLUSION: Baseline thyroid function, as measured by serum TSH, may predict a patient's response to antidepressant treatment with SSRIs. Optimal thyroid function, beyond simply being within the normal laboratory values, may be necessary for an optimal response to antidepressants.     

Spinal delivery of analgesics in experimental models of pain and analgesia

Systemic administration of analgesics can lead to serious adverse side effects compromising therapeutic benefit in some patients. Information coding pain transmits along an afferent neuronal network, the first synapses of which reside principally in the spinal cord. Delivery of compounds to spinal cord, the intended site of action for some analgesics, is potentially a more efficient and precise method for inhibiting the pain signal. Activation of specific proteins that reside in spinal neuronal membranes can result in hyperpolarization of secondary neurons, which can prevent transmission of the pain signal. This is one of the mechanisms by which opioids induce analgesia. The spinal cord is enriched in such molecular targets, the activation of which inhibit the transmission of the pain signal early in the afferent neuronal network. This review describes the pre-clinical models that enable new target discovery and development of novel analgesics for site-directed pain management.