Neurosurgical Injuries Associated With the Use of Personal Watercrafts.

INTRODUCTION:  A personal watercraft is widely used for recreation on coastlines, rivers, and lakes. This study aimed to identify the spectrum of neurosurgical injuries related to personal watercraft accidents in Puerto Rico. METHODS: A retrospective study was performed utilizing the University of Puerto Rico neurosurgery database to identify patients who had been consulted to the neurosurgery service from 2005 to 2023 due to a personal watercraft-related neurosurgical injury. For each identified patient, basic demographics, injuries received, Glasgow coma scale score at arrival, American Spinal Injury Association impairment scale grade, surgery performed, and outcome upon discharge using the modified Rankin scale (mRS) score were collected. Descriptive statistics were used to report frequency and mean values. RESULTS: Our service evaluated 11 patients with a personal watercraft-related neurosurgical injury diagnosis during the study period. The mean age of the patients was 35 (± 9). Around 82% of the patients were males. Ejection from the personal watercraft was the mechanism of the trauma in 73% of the patients. Three patients were impacted by a personal watercraft. There were seven spinal injuries and four brain injuries. Among the spinal injured patients, two had neurological deficits. None of the patients with brain trauma required urgent surgery; however, three arrived intubated. Two of them showed signs of diffuse axonal injuries on the head CT scan, while the other had multiple brain contusions. Upon discharge, 70% of the patients had a mRS grade of 0-3. CONCLUSIONS: Personal watercraft accidents causing significant neurological injuries to the brain and spine are infrequent. Injuries were more prevalent among male patients in their thirties. Most patients showed good outcomes when discharged from the hospital. Moderate to severe disability occurred more frequently among spinal injured patients due to residual deficits requiring assistance for ambulation and activities of daily living.

Testicular yolk sac tumour metastasis to the L2 vertebra.

The role of surgery for metastases to the vertebra from yolk sac tumours has not been established. The main treatment for disseminated disease is chemotherapy. We present a man in his 30s with a left orchiectomy for a testicular mixed germ cell tumour with a prominent yolk sac component who, 12 months later, developed an asymptomatic metastasis to the L2 vertebra unresponsive to chemotherapy and radiotherapy. The patient underwent resection of the L2 vertebral body, leaving a small residual tumour anterior to the vertebra attached to the great vessels. Pathology confirmed the diagnosis of a metastatic testicular yolk sac tumour in the vertebra. The postoperative MRI 6 months later demonstrated significant expansion of the tumour at the soft tissues anterior to the expandable titanium cage encasing the great vessels and extending to the paraspinal areas. Additional salvage surgery was not recommended because of the advanced stage of the tumour.

Prognosis and Outcome of Cervical Primary Extraosseous Intradural Extramedullary Ewing Sarcoma: A Systematic Review.

Primary spinal extraosseous Ewing sarcoma (ES) is a rare mesenchymal tumor characterized by high malignancy, occurring in a few patients with ES. The occurrence of this tumor in the intradural extramedullary spinal region is infrequent. This systematic review examines primary extraosseous intradural extramedullary ES in the cervical region to provide specific outcomes and evaluate the role of adjuvant chemoradiation in overall prognosis. A systematic review was conducted to identify all cervical primary extraosseous intradural extramedullary ES reported in the literature. The search included the databases of PubMed, Google Scholar, Medline, Embase, and Scopus from inception to June 2021. Inclusion criteria include a reported death outcome or a minimum one-year follow-up. Our search retrieved 21 articles that involved the cervical spine, but only 11 cases met the inclusion criteria. Of the nine patients who demonstrated disease progression, six experienced local failure, two had distant craniospinal axis failure, and one had systemic metastases. Five patients died of the disease at a median of 11 months after diagnosis. Our analysis showed a one-, two-, and five-year progression-free survival (PFS) of 36.4%, 36.4%, and 12.1%, respectively. The one-, two-, and five-year overall survival rates were 72.7%, 62.3%, and 46.8%, respectively. Three of the five (60%) patients who died received craniospinal radiotherapy. Of the six patients who survived, two received craniospinal radiotherapy (33%), and one received whole spine radiotherapy (17%). This review showed that patients with cervical primary extraosseous intradural extramedullary ES had poor progression-free survival and overall survival rates. The addition of adjunct craniospinal radiotherapy did not improve the prognosis of these patients.

Time of Surgery in the Outcome of Cervical Spinal Cord Injury: the University of Puerto Rico Experience.

OBJECTIVE: The purpose of this study was to determine the effect of the timing of surgery on the neurological function of patients with a cervical spinal cord injury. METHODS: Retrospectively, an analysis was done of patients who underwent decompression and/or spinal cord stabilization surgeries from 2010 through 2014 for cervical trauma. All patients were older than 18 years of age, had had surgery at our facility, and had made at least 1 follow-up visit. American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores were compared for patients who underwent early surgeries (less than 72 hours after trauma) and for those who underwent late surgeries (more than 72 hours after trauma). RESULTS: There were a total of 107 patients. Sixty-two patients had spinal cord injuries. The average age was 38.6 years, and 84% of the participants were male. The most common mechanism of trauma was motor vehicle accident. Twenty-nine percent of the patients developed neurogenic shock and 27% experienced respiratory failure during the first week after admission. Seventeen patients died during the study period. A multivariate analysis of AIS score improvement revealed that the only significant factor was incomplete neurological injury. There was no significant difference in the percentage of patients that improved with early surgery compared to that of those that improved after late surgery. CONCLUSION: Traumatic cervical spinal cord injury is associated with high mortality and morbidity. Early surgery was not associated with an improved neurological outcome at long-term follow-up. The benefit of early surgery was seen only in terms of decreasing each patient's length of hospital stay.

Anterior Longitudinal Ligament Release From the Minimally Invasive Lateral Retroperitoneal Transpsoas Approach: Technical Note.

BACKGROUND: The technique for minimally invasive anterior longitudinal ligament release is a major advancement in lateral access surgery. This method provides hypermobility of lumbar segments to allow for aggressive lordosis restoration while maintaining the benefits of indirect decompression and minimally invasive access. OBJECTIVE: To provide video demonstration of the lateral retroperitoneal transpsoas approach with anterior longitudinal ligament sectioning. METHODS: A detailed surgical technique of the minimally invasive anterior column release is described and illustrated in an elderly patient with adult spinal deformity and low back pain (visual analog scale, 8 of 10) refractory to conservative measures. The 3-foot standing radiographs demonstrated a lumbar lordosis of 54.4°, pelvic incidence of 63.7°, and pelvic tilt of 17.5°. Computed tomography and magnetic resonance imaging showed generalized lumbar spondylosis and degenerative disc changes from L2 to L5. RESULTS: The patient underwent a multilevel minimally invasive deformity correction with an anterior longitudinal ligament release at the L3/L4 level through the lateral retroperitoneal transpsoas approach. Lumbar lordosis increased from 54.4° to 77° with a global improvement in sagittal vertical axis from 4.37 cm to 0 cm. Total blood loss was less than 25 mL, and there were no major neurological or vascular complications. CONCLUSION: The anterior longitudinal ligament release using the minimally invasive lateral approach allows for deformity correction without the morbidity and blood loss encountered by traditional open posterior approaches. However, the risk of major vascular/visceral complication warrants only experts in minimally invasive lateral surgery to attempt this technique.

Complications and neurological deficits following minimally invasive anterior column release for adult spinal deformity: a retrospective study.

BACKGROUND: Minimally invasive techniques have become increasing popular and are expanding into deformity surgery. The lateral retroperitoneal transpsoas anterior column release (ACR) is a newer minimally invasive alternative to posterior osteotomy techniques for correcting and promoting global spinal alignment. This procedure attempts to avoid the potential complications associated with conventional osteotomies, but has its own subset of unique complications to be discussed in depth. METHODS: A retrospective review was performed in all patients who underwent the minimally invasive (MIS) ACR procedure from 2010 to present at our institution. All perioperative and postoperative complications were recorded by an independent reviewer. Demographics, spinopelvic parameters, and operative data were collected. The primary etiologic diagnosis was adult spinal deformity. Spinopelvic parameters were measured based on standing 36-inch scoliosis films. RESULTS: Thirty-one patients underwent a total of 47 MIS-ACRs. The mean age of the cohort was 62. Mean follow up was 12 months (range 3-38 months). The average change from in lumbar lordosis (LL) was 17.6°, in pelvic tilt was 4.3°, coronal Cobb was 13.9 and in SVA was 3.8 cm. Of the 47 MIS-ACR procedures, there were 9 (9/47, 19 %) major complications related to the ACR. Iliopsoas weakness was seen in eight patients and retrograde ejaculation in one patient. Only one patient remained with mild motor deficit at the most recent follow-up. No revision surgeries were required for the anterolateral approach. There was no vascular, visceral, or infectious complications associated with the MIS-ACR. CONCLUSION: The MIS-ACR is one of the most technically demanding procedures performed from the lateral transpsoas approach. This procedure has the advantage of maintaining and improving spinal global alignment while minimizing blood loss and excessive tissue dissection. It comes with its own unique set of potentially catastrophic complications and should only be performed by surgeons proficient in both deformity correction and the lateral approach.

Percutaneous Minimally Invasive (MIS) Guide Wire-less Self-Tapping Pedicle Screw Placement in the Thoracic and Lumbar Spine: Safety and Initial Clinical Experience: Technical Note.

BACKGROUND: Multiple methods for minimally invasive (MIS) thoracic and lumbar pedicle screw placement exist. The guide wire is almost universally used for most insertion techniques; however, its use is not without complication and potentially prolongs surgical procedures. OBJECTIVE: To evaluate the safety of percutaneous MIS guide wire-less pedicle screw placement in the thoracic and lumbar spine at a single institution over a 3-year experience. METHODS: Forty-one patients who underwent posterior instrumentation with 110 transpedicular MIS thoracic and lumbar screws by a single surgeon from 2011 to 2014 were analyzed. The mean age was 63 years at the time of surgery. Etiological diagnoses were adult spinal deformity, trauma, spondylosis/spondylolisthesis, and other spinal diseases. Pedicle screws were inserted with the use of a guide wire-free technique in which anatomy-specific entry sites and fluoroscopic landmarks were used to guide the surgeon. A square, sharp-tipped pedicle screw was carefully advanced under biplanar fluoroscopic image (anteroposterior and lateral) down the pedicle into the body. No tapping or any type of electromonitoring was performed. An independent spine surgeon using medical records and thoracic/lumbar computed tomography taken during the postoperative period reviewed all patients. RESULTS: The number of the screws inserted at each level was as follows: total, 110; thoracic, 30; and lumbar, 80. All screws were evaluated by computed tomography to assess screw position. Seven screws (6.3%) were inserted with moderate cortical perforation, including 3 screws (2.7%) that violated the medial wall. There were no neurological, vascular, or visceral complications with up to 3 years of follow-up. CONCLUSION: The percutaneous MIS guide wire-less technique of lumbar and thoracic pedicle screw placement performed using a biplanar fluoroscopic guidance in a stepwise, consistent manner is an accurate, safe, and reproducible method of insertion to treat a variety of spinal disorders.

Subsidence of polyetheretherketone intervertebral cages in minimally invasive lateral retroperitoneal transpsoas lumbar interbody fusion.

STUDY DESIGN: A retrospective review. OBJECTIVE: The objective is to evaluate subsidence related to minimally invasive lateral retroperitoneal lumbar interbody fusion by reviewing our experience with this procedure. SUMMARY OF BACKGROUND DATA: Polyetheretherketone intervertebral cages of different lengths, widths, and heights filled with various allograft types are commonly used as spacers in lumbar fusions. Subsidence is a potential complication. To date, there are no published reports specifically addressing subsidence, because it relates to a series of patients undergoing minimally invasive lateral retroperitoneal transpsoas lumbar interbody fusion. METHODS: An institutional review board-approved, retrospective review of a prospectively collected database was conducted. One hundred forty consecutive patients who underwent this procedure between L1 and L5 during a 2-year period were included. All patients had T scores of -2.5 or more. Postoperative radiographs during routine follow-ups were reviewed for subsidence, defined as any violation of the vertebral end plate. RESULTS: Radiographical subsidence occurred in 14.3% (20 of 140), whereas clinical subsidence occurred in 2.1%. Subsidence occurred in 8.8% (21 of 238) of levels fused. Construct length had a significant positive correlation with increasing subsidence rates. Subsidence rates decreased progressively with lower levels in the lumbar spine, but had a higher than expected rate at L4-L5. Subsidence rates of 14.1% (19 of 135) and 1.9% (2 of 103) were associated with 18-and 22-mm-wide cages, respectively. No significant trends were observed with cage lengths. Supplemental lateral plates had a higher rate of subsidence than bilateral pedicle screws. Subsidence occurred at the superior end plate 70% of the time. CONCLUSION: The use of wider intervertebral cages leads to a significantly lower rate of subsidence, but a longer cage does not necessarily offer a similar advantage. Wide cages are protective against subsidence, and the widest cages should be used whenever feasible for interbody fusion in the lumbar spine to protect indirect compression and promote arthrodesis.

Acute adrenal insufficiency in cervical spinal cord injury.

BACKGROUND: Adequate adrenal response is fundamental for the maintenance of physiological homeostasis in the setting of trauma and severe illness. Patients with neurogenic shock are at risk of severe consequences if adrenal insufficiency (AI) is not rapidly identified and treated. OBJECTIVE: To analyze the incidence of AI in patients with acute cervical spinal cord injury and its effect on in-hospital complications. METHODS: The medical records of patients older than 18 years who were admitted to the adult neurosurgery service at the University District Hospital as the result of neurogenic shock after acute cervical spinal cord injury from January 2004 to December 2009 were reviewed retrospectively. RESULTS: One hundred ninety-nine patients were admitted with acute cervical spinal cord injury. A total of 37 patients met the pre-established criteria for neurogenic shock. The incidence of AI in patients with neurogenic shock was 22%. The average random cortisol was 9.3 µg/dL in patients with AI versus 29.2 µg/dL in non-AI. The presence of AI was positively correlated with complications and an increase in the risk of intubation (P = 0.01 and P = 0.002). The 30-day mortality rate in patients with AI was 13% compared with the 3% in the non-AI group (P = 0.39). CONCLUSIONS: Adrenal insufficiency is a poorly recognized complication in patients with acute cervical spinal cord injury and its aggressive treatment is of utmost importance to avoid further neurological injury.

A 10-year experience of radiosurgical treatment for cerebral arteriovenous malformations: a perspective from a series with large malformations. Clinical article.

OBJECT: The purpose of this study was to describe a 10-year experience in the use of radiosurgery (RS) for patients with arteriovenous malformations (AVMs) in Puerto Rico. METHODS: This retrospective analysis was performed for all patients with AVMs treated with RS by the senior author (R.H.B.) in Puerto Rico. Between February 1999 and December 2009, a total of 83 patients underwent the procedure. All charts were reviewed for recollection of demographic data, and AVM and treatment characteristics. Clinical and radiographic follow-up information was collected retrospectively. RESULTS: Eighty-three patients were treated and 86 RS procedures for AVMs were performed during a 10-year period. Eight patients were lost to follow-up. The remaining 75 patients included 36 males and 39 females, whose median age was 34.5 years. Hemorrhage was the initial presentation in 40% of patients. Fifty-seven AVMs (73%) were treated previously with endovascular neurosurgery, without success. The median volume of the malformation was 17.7 ml. Nearly 65% of the malformations were considered large (≥ 10 ml) in volume. Forty patients had AVMs with largest diameter ≥ 3.5 cm. The overall obliteration rate was 56.4%, and the median time for obliteration was 29 months. The AVMs ≥ 3.5 cm in diameter had a greater latency period than those < 3.5 cm (31 months vs 46 months, respectively; p = 0.01). In addition, AVM obliteration was inversely associated with its volume, especially in large lesions (p = 0.037). In bivariate analysis, patients achieving obliteration had lower Spetzler-Martin scores compared with patients in whom obliteration was not achieved (p = 0.009). Postradiosurgery hemorrhages were seen in 9 cases. Eleven patients underwent surgery after RS. Major neurological deficits developed in 9 patients, whereas 17 had only minor deficits. The occurrence of neurological deficits was significantly associated with lesions with volume ≥ 10 ml. CONCLUSIONS: Radiosurgery is a reasonable treatment option for AVMs in the majority of cases, in spite of the large, difficult-to-treat malformations.

Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction.

G-CSF induced mobilisation of progenitor cells is a multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on haematopoietic cells. This study's aim was to investigate progenitor cells mobilised during myocardial infarction after treatment with granulocyte-stimulating factor (G-CSF). In the randomised, double-blind, placebo-controlled REVIVAL-2 study, 114 patients with acute myocardial infarction were included. Five days after successful percutaneous coronary intervention patients received either 10 microg/kg G-CSF (n=56) or placebo (n=58) subcutaneously for five days. Venous blood samples were analysed on day(s) 1, 3, 5 and 7 after therapy, and progenitor cell mobilisation and surface expression of VLA-4, LFA-1 and CXCR-4 was measured on circulating progenitor cells using flow cytometry. G-CSF induced a significant increase in circulating progenitor cells (72 +/- 20 cells/microl vs. 4.5 +/- 0.8 cells/microl, p<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on progenitor cells was decreased by 44%, 49% and 60% after G-CSF as compared to placebo (p<0.05). In accordance, mRNA expression of CXCR4 was reduced. Moreover, anti-proliferative transducer of ERB (TOB) mRNA was decreased, suggesting an increased proliferative potential of the mobilised progenitor cells. Decreased expression of adhesion and chemokine receptors on G-CSF mobilised progenitor cells in acute myocardial infarction may alter the homing capacity of circulating cells to the myocardium.

Descriptive profile of surgically-confirmed adult central nervous system tumors in Puerto Rico.

INTRODUCTION: Published studies regarding the incidence of central nervous system (CNS) tumors in Puerto Rico (PR) are exceedingly rare. The general understanding is that the incidence of these tumors in Puerto Rico is similar to the one found in the United States of America (USA). The objective of this study is to describe the specific profile of all the CNS tumors that are surgically intervened in Puerto Rico, through the creation of a database. METHODS: A retrospective analysis of all the surgical procedures from January 1, 2002 to May 31, 2006 for adult CNS tumors in Puerto Rico was performed. Each case was evaluated for demographic information, operative procedure, lesion description and official pathological report. Recurrent lesions were excluded. The information was organized to form a database of all the CNS neoplasms. RESULTS: A total of 1,018 procedures for CNS tumors were performed on 1,005 patients. The incidence rate of surgically intervened CNS tumors in Puerto Rico is 6 per 100,000 people. CNS tumors were more common in women than in men (58% vs. 42%), respectively. The mean age was 52.4 years. The most common histological type found was meningioma WHO I (24%), followed by pituitary adenomas (16%), and glioblastoma multiforme (14%). CONCLUSIONS: Our results reflect a unique histopathological distribution of operated CNS tumors in Puerto Rico. In this series, primary tumors are more common than metastatic tumors. Benign histological tumors were more frequent than more malignant variants. Although this study reflects only the histologically diagnosed tumors, it is headway towards diagnosing the incidence of all CNS tumors in Puerto Rico.

A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days.

AIMS: We sought to test whether an increase in the clopidogrel maintenance dose results in increased inhibition of platelet aggregation. METHODS AND RESULTS: Sixty patients after pre-treatment with 600 mg of clopidogrel and within 12 h after successful PCI were included in this trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a double-blind randomized manner. Platelet function was evaluated 30 days after the intervention with optical aggregometry and with a new point-of-care test (VerifyNowtrade mark P2Y12 assay). Maximal 5 microM ADP-induced platelet aggregation 30 days after PCI in the group treated with 150 mg/day clopidogrel (45.1 +/- 20.9%) was significantly lower than in the group treated with 75 mg/day (65.3 +/- 12.1%; P < 0.001). The VerifyNowtrade mark P2Y12 assay also indicated a higher degree of platelet function inhibition in the group treated with 150 mg/day (60.0 +/- 72.0 P2Y12 Reaction Units) than in the group treated with 75 mg/day (117.0 +/- 64.3 P2Y12 Reaction Units; P = 0.004). CONCLUSION: Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense inhibition of platelet aggregation than administration of the currently recommended 75 mg maintenance dose.

Contribution of mesenterial muscle dedifferentiation to intestine regeneration in the sea cucumber Holothuria glaberrima.

Holothurians (sea cucumbers) have been known from ancient times to have the capacity to regenerate their internal organs. In the species Holothuria glaberrima, intestinal regeneration involves the formation of thickenings along the free mesentery edge; these thickenings will later give rise to the regenerated organ. We have previously documented that a remodeling of the extracellular matrix and changes in the muscle layer occur during the formation of the intestinal primordium. In order to analyze these changes in depth, we have now used immunocytochemical techniques and transmission electron microscopy. Our results show a striking disorganization of the muscle layer together with myocyte dedifferentiation. This dedifferentiation involves nucleic activation, disruptions of intercellular junctions, and the disappearance of cell projections, but more prominently, the loss of the contractile apparatus by the formation and elimination of spindle-like structures. Muscle dedifferentiation can be seen as early as 2 days following evisceration and continues during the next 2 weeks of the regeneration process. Dedifferentiation of myocytes might result in cells that proliferate and give rise to new myocytes. Alternatively, dedifferentiating myocytes could give rise to cells with high nuclear-to-cytoplasmic ratios, with some being eliminated by apoptosis. Our results, together with those in other regeneration models, show that myocyte dedifferentiation is a common event in regeneration processes and that the dedifferentiated cells might play an important role in the formation of the new tissues or organs.

A randomized, double-blind, placebo-controlled trial on restenosis prevention by the receptor tyrosine kinase inhibitor imatinib.

OBJECTIVES: The aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a systemic imatinib treatment, a potent platelet-derived growth factor (PDGF) receptor kinase inhibitor, for the prevention of recurrent restenosis in patients with in-stent restenosis (ISR). BACKGROUND: Neointima proliferation after stent placement has been associated with the effect of potent mitogenes such as PDGF, and their inhibition has resulted in reduction of neointima formation in experimental models. METHODS: A total of 180 patients with either symptoms or a positive stress test in the presence of angiographically significant ISR were randomly assigned to two treatment arms: imatinib treatment or placebo. Patients received imatinib (600 mg/day) for 10 days starting 2 days before repeat intervention. Angiographic restenosis at follow-up angiography was the primary end point of the study. RESULTS: Repeat angiography was performed in 160 of 180 patients (88.9%). The combined rate of death or MI at one year was 1.0% in patients randomized to either group (p = 0.67). Compared with the placebo group, imatinib treatment did not affect the angiographic restenosis rate (38.8% with imatinib vs. 41.3% with placebo; p = 0.75). Similarly, the need for target lesion revascularization did not differ between both groups (28.1% with imatinib vs. 28.6% with placebo; p = 0.94). CONCLUSIONS: Systemic imatinib therapy does not affect the risk of recurrence in patients with ISR.

Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial.

BACKGROUND: For patients undergoing percutaneous coronary intervention, the administration of a clopidogrel loading dose ranging from 300 to 600 mg is currently recommended. It is unknown, though, whether loading doses higher than 600 mg exert additional suppression of platelet function. METHODS AND RESULTS: Sixty patients with suspected or documented coronary artery disease admitted to our hospital for coronary angiography were included in this trial. They were allocated to 1 of 3 clopidogrel loading doses (300, 600, or 900 mg) in a double-blinded, randomized manner. Plasma concentrations of the active thiol metabolite, unchanged clopidogrel, and the inactive carboxyl metabolite of clopidogrel were determined before and serially after drug administration. Optical aggregometry was performed before and 4 hours after administration of clopidogrel. Loading with 600 mg resulted in higher plasma concentrations of the active metabolite, clopidogrel, and the carboxyl metabolite compared with loading with 300 mg (P< or =0.03) and lower values for adenosine diphosphate-induced (5 and 20 micromol/L) platelet aggregation 4 hours after drug administration (P=0.01 and 0.004). With administration of 900 mg, no further increase in plasma concentrations of active metabolite and clopidogrel (P> or =0.38) and no further suppression of adenosine diphosphate-induced (5 and 20 micromol/L) platelet aggregation 4 hours after drug administration was achieved when compared with administration of 600 mg (P=0.59 and 0.39). CONCLUSIONS: Single doses of clopidogrel higher than 600 mg are not associated with an additional significant suppression of platelet function because of limited clopidogrel absorption.

Myogenesis during holothurian intestinal regeneration.

Echinoderms are well known as being able to regenerate body parts and thus provide excellent models for studying regenerative processes in adult organisms. We are interested in intestinal regeneration in the sea cucumber, Holothuria glaberrima, and focus here on the regeneration of intestinal muscle components. We have used immunohistochemical techniques to describe the formation of the intestinal muscle layers. Myoblasts are first observed within the regenerating structure, adjacent to the coelomic epithelia. Within a few days, these cells acquire muscle markers and form a single cell layer that underlies the epithelia. Animals injected with BrdU at various regeneration stages have been subsequently analyzed for the presence of muscle differentiation markers. BrdU-labeled muscle nuclei are observed in myocytes of 3-week regenerates, showing that these cells originate from proliferating precursors. The peak in muscle precursor proliferation appears to occur during the second week of regeneration. Therefore, new muscle cells in the regenerating intestine originate from precursors that have undergone cell division. Our results suggest that the precursor cells arise from the coelomic epithelia. We also provide a comparative view of muscle regeneration in an echinoderm, a topic of interest in view of the many recent studies of muscle regeneration in vertebrate species.

Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis: the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis (OSIRIS) trial.

BACKGROUND: Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR. METHODS AND RESULTS: Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P<0.001). CONCLUSIONS: In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.