Hip Labral Reconstruction: Techniques and Outcomes.

PURPOSE OF REVIEW: With increased understanding of the biomechanical function of the acetabular labrum, more attention has been directed towards surgical techniques that preserve or restore normal joint anatomy. While labral repair has been shown to produce superior outcomes to labral debridement, repair is not always possible in the setting of severe labral intrasubstance tearing or deficiency. These patients were previously left without suitable arthroscopic treatment options. RECENT FINDINGS: Labral reconstruction is an emerging procedure that has been shown to offer promising outcomes for traditionally difficult-to-treat hip pathology. Short- and mid-term follow-up studies have consistently demonstrated significant improvement in patient-reported outcomes, function, and patient satisfaction postoperatively, often despite less favorable preoperative characteristics. Labral reconstruction is a viable arthroscopic treatment option that has been shown to reliably produce clinically meaningful results in patients with severe labral pathology that is not amenable to repair/refixation or augmentation.

Epidermal growth factor-induced cytoprotection in human intestinal cells involves intracellular calcium signaling.

BACKGROUND: The mechanism(s) whereby epidermal growth factor (EGF) protects against cellular injury remains poorly understood. Previous data in our laboratory have suggested that EGF-induced cellular proliferation in human colonic carcinoma cells (Caco-2) may involve changes in intracellular calcium content ([Ca(2+)](i)). Our current objective was to determine if a similar process was involved with EGF-induced cytoprotection. METHODS: Postconfluent Caco-2 cells were employed for all experimentation. [Ca(2+)](i) was measured with Fluo-3 fluorescence. Injury was measured employing Ethidium homodimer 1 uptake and lactate dehydrogenase (LDH) release. RESULTS: Caco-2 cells pretreated, but not concomitantly treated, with EGF (10-100 ng/ml, 30-60 min) significantly attenuated cellular injury induced subsequently by 500 microM deoxycholate (DC). Cells exposed to 100 ng/ml EGF demonstrated an initial increase in [Ca(2+)](i) (1-5 min) which was blocked with neomycin, an inhibitor of inositol 1,4,5-trisphosphate (IP(3)) generation, and the phospholipase C (PLC) inhibitor U73122, but not U73343 (inactive control). This was followed by sustained extracellular Ca(2+) influx (5-20 min), which was attenuated with calcium-free buffer and the store operated Ca(2+) channel blocker La(3+). [Ca(2+)](i) then returned to baseline (20-30 min), a process blocked with the Ca(2+)-ATPase inhibitors quercetin and vanadate. The above treatments, which in and of themselves did not induce cellular injury, were repeated and cells were subsequently exposed to DC. All groups exposed to 500 microM DC demonstrated significant increases in both Ethidium Homodimer 1 uptake and LDH release. Both indices of injury were significantly decreased when cells were pretreated with EGF +/- the inactive PLC inhibitor U73343. However, protection induced by EGF was lost when any of its effects on changes in [Ca(2+)](i) were prevented: internal Ca(2+) store release via PLC and IP(3), sustained Ca(2+) influx through store operated Ca(2+) channels, or subsequent Ca(2+) efflux. CONCLUSION: Taken together, these data strongly suggest that the cytoprotective effects of EGF may involve Ca(2+) signaling.

Treatment of refractory chylothorax with externalized pleuroperitoneal shunts in children.

BACKGROUND: Traditional therapy for refractory chylothorax in the pediatric population has included pleurodesis and thoracic duct ligation. These procedures are associated with high morbidity and questionable success rates. METHODS: We retrospectively reviewed our experience with 15 patients who underwent treatment for chylous effusions using pleuroperitoneal shunts with exteriorized pump chambers. Mean patient age at time of shunt placement was 2.1 (0.1 to 11.5) years and the most common indication (7 of 15) was refractory chylothorax following surgical correction of congenital heart disease. Mean chylothorax duration before shunt placement was 76 (5 to 810) days and shunts were in place for an average of 104 (12 to 365) days. A total of 19 chylous effusions (pleural or pericardial) were treated with shunts. RESULTS: Nine of 11 right-sided chylothoraces, 5 of 6 left-sided chylothoraces, and 2 of 2 chylopericardia resolved with shunt therapy (84% total). Pleuroperitoneal shunting failed to clear the effusion in 3 children. There were six episodes of shunt malfunction that were repaired and two episodes of infection. Inguinal or umbilical hernia developed in 4 patients. CONCLUSIONS: Externalized pleuroperitoneal shunting is a safe, effective, and minimally invasive treatment for children with refractory chylous effusions.

Calcium accentuates injury induced by ethanol in human gastric cells.

The mechanism(s) whereby ethanol induces cellular injury remains poorly understood. Furthermore, the role of calcium in gastric mucosal injury under in vitro conditions is poorly defined. The major objectives of this study were to (1) define the temporal relationship between intracellular calcium accumulation induced by ethanol and cellular injury, (2) characterize the mechanism(s) whereby ethanol increases cellular calcium content, and (3) determine whether calcium removal would attenuate ethanol-induced cellular injury. Human gastric cells (AGS) were used for all experiments. Sustained intracellular calcium accumulation induced by ethanol, but not transient changes, preceded and directly correlated with cellular injury. Cells exposed to damaging concentrations of ethanol demonstrated an initial calcium surge that appeared to be a consequence of inositol 1,4,5-triphosphate (IP3) generation and subsequent internal store release followed by a sustained plateau resulting from extracellular calcium influx through store-operated calcium channels. Finally, both morphologic (cellular injury) and functional (clearance of bovine serum albumin) changes induced by ethanol were significantly attenuated when extracellular Ca(+&plus) influx was prevented, and further decreased when intracellular Ca(++) stores were depleted. These data indicate that calcium plays a significant role in cellular injury induced by ethanol.

Nonsteroidal anti-inflammatory drugs attenuate epidermal growth factor-induced proliferation independent of prostaglandin synthesis inhibition.

BACKGROUND: The mechanism(s) whereby nonsteroidal anti-inflammatory drugs (NSAIDs) attenuate colorectal tumor growth remains poorly understood. This study determined if NSAIDs decreased epidermal growth factor (EGF)-induced proliferation in human colonic tumor (Caco-2) cells and whether this process involved the inhibition of prostaglandin (PG) synthesis. METHODS: Caco-2 cells were serum-starved (48 h) and subsequently treated (48 h) with either serum-free media or EGF (10 ng/ml) +/- physiologic and noninjurious (as determined by LDH release) concentrations of aspirin, indomethacin, and ibuprofen. PG synthesis was measured by EIA. Proliferation was quantitated with two assays: cellular protein and nucleic acid content. RESULTS: NSAID treatment did not inhibit growth in cells treated with only serum-free media. Cells exposed to EGF demonstrated a significant increase in PGE2, protein, and nucleic acid. Levels of other eicosanoids (PGI2, TXA2) were minimal both before and after EGF treatment. Despite varying degrees of PGE2 inhibition, each NSAID group equally attenuated EGF-induced protein and nucleic acid synthesis. The correlation between PGE2 levels and protein (R2 = 0.56) or nucleic acid (R2 = 0.54) was poor. Finally, the addition of a physiologically appropriate concentration of exogenous PGE2 failed to reverse NSAID-induced growth inhibition. CONCLUSION: These data suggest that NSAIDs, independent of PG synthesis inhibition, attenuate EGF-induced proliferation in Caco-2 cells. This may provide one explanation for how NSAIDs limit colonic neoplasia.

A simplified method for studying hypoxia and reoxygenation injury under in vitro conditions.

A hypoxia chamber was constructed which allowed for the sequential sampling and blood gas analysis of buffer bathing cells in culture which were subjected to graded periods of hypoxia. Following hypoxia, the human fetal small intestinal cells (CCL-241) were placed into a normoxic environment for the remainder of a 24 h study period. A cytotoxicity assay revealed significant mortality in cells subjected to hypoxia and reoxygenation, but not in those subjected to hypoxia alone. Analysis of lactate dehydrogenase release into buffer samples also indicated a greater cellular injury among cells exposed to hypoxia and reoxygenation. Additionally, levels of lipid peroxidation products were found to be significantly elevated in cells exposed to periods of hypoxia followed by reoxygenation, but not hypoxia alone, as measured by a thiobarbituric acid fluorometric assay. This suggests that lipid peroxidation mediated by oxygen-derived free radical species is the mechanism of injury in these cells. This study demonstrates that such a chamber provides a more precise way to monitor hypoxia and is a useful tool for studying hypoxia and reoxygenation under in vitro conditions.

Indomethacin increases susceptibility to injury in human gastric cells independent of PG synthesis inhibition.

Indomethacin and other nonsteroidal anti-inflammatory drugs are commonly used to indirectly deduce the possible role of PGs in a process being studied. The objective of this study was to determine if indomethacin, at concentrations comparable to plasma and tissue levels obtained in humans taking therapeutic doses, predisposes human gastric cells to injury through inhibition of PGs or acts through an alternate mechanism. The role of intracellular Ca2+ in this damaging process was also assessed. Indomethacin pretreatment, although by itself nondamaging, was associated with elevated intracellular Ca2+ concentrations and an increased cellular permeability, an effect that was dependent on extracellular Ca2+. Furthermore, indomethacin pretreatment significantly predisposed AGS cells to injury induced by two dissimilar agents (deoxycholate and A-23187), both of which are associated with intracellular Ca2+ accumulation. The addition of exogenous PGs did not reverse the predisposition to injury induced by indomethacin. The observed effects of indomethacin were dependent on concentration and not on ability to inhibit PG synthesis. Similar effects were not observed with equipotent concentrations of ibuprofen or aspirin. Finally, the exacerbation of deoxycholate-induced injury induced by indomethacin was not observed when extracellular Ca2+ was removed. Indomethacin, by disturbing intracellular Ca2+ homeostasis, predisposes human gastric cells to injury through mechanisms independent of PG synthesis. The current study suggests that data resulting from studies employing only indomethacin as a PG synthesis inhibitor should be interpreted with caution.

Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells.

We have developed an in vitro model of adaptive cytoprotection induced by deoxycholate (DC) in human gastric cells and have shown that pretreatment with a low concentration of DC (mild irritant, 50 microM) significantly attenuates injury induced by a damaging concentration of DC (250 microM). This study was undertaken to assess the effect of the mild irritant on changes in intracellular Ca2+ and to determine if these perturbations account for its protective action. Protection conferred by the mild irritant was lost when any of its effects on intracellular Ca2+ were prevented: internal Ca2+ store release via phospholipase C and inositol 1,4, 5-trisphosphate sustained Ca2+ influx through store-operated Ca2+ channels or eventual Ca2+ efflux. We also investigated the relationship between Ca2+ accumulation and cellular injury induced by damaging concentrations of DC. In cells exposed to high concentrations of DC, sustained Ca2+ accumulation as a result of extracellular Ca2+ influx, but not transient changes in intracellular Ca2+ content, appeared to precede and induce cellular injury. We propose that the mild irritant disrupts normal Ca2+ homeostasis and that this perturbation elicits a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.

Case report of an intracarotid amobarbital procedure performed for a deaf patient.

The intracarotid amobarbital procedure (IAP) was conducted with a profoundly deaf young man prior to right anteromedial temporal lobectomy for pharmacologically refractory partial complex seizures. The IAP required considerable modification in order to take into account the use of varying sign language methods and related issues. Visual memory, American Sign Language, signed English, and finger-spelling functioning were all assessed. The patient manifested left hemisphere dominance for all these abilities, performing well under right hemisphere anesthesia. In contrast, no ability to function on these tasks was detectable when the left hemisphere was anesthetized. This demonstrates that an intact left temporal lobe and related structures are sufficient to support sign language functioning. The development of a deaf adaptation of the IAP is of methodological significance, as the IAP is thereby rendered accessible for deaf patients.

Cortical reorganization in deaf children.

Topographic mapping of the cerebral cortex of 79 deaf children and a group of matched hearing children was performed, using measures of electroencephalographic coherence, phase, and power. Deaf children manifested higher coherence and lower phase in certain left hemispheric areas, suggesting less neural differentiation; but lower coherence and higher phase in certain right hemispheric areas, suggesting greater differentiation. Deaf children had higher total power in bilateral frontal cortex than did hearing children. The data also suggested compensatory functioning in the visual cortex of the deaf subjects. The pattern of results varied somewhat in relation to cause of deafness. These findings support the hypothesis that prelingual deafness results in a partial reorganization of cerebral cortex.