Carbon Dioxide, Blood Pressure, and Perioperative Stroke: A Retrospective Case-Control Study.

BACKGROUND: The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke. METHODS: We conducted a retrospective, case-control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve. The association between stroke and total area under the curve values was then tested while adjusting for relevant confounders. RESULTS: In total, 1,244,881 cases were analyzed. Among the cases that screened positive for stroke (n = 1,702), 126 were confirmed and successfully matched with 500 corresponding controls. Total area under the curve was significantly associated with stroke for all thresholds tested, with the strongest combination observed with mean arterial pressure less than 55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% CI, 1.10 to 1.23], P < 0.0001) and end-tidal carbon dioxide 45 mmHg or greater (adjusted odds ratio per 10 mmHg-min, 1.11 [95% CI, 1.10 to 1.11], P < 0.0001). There was no interaction effect observed between blood pressure and carbon dioxide. CONCLUSIONS: Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk.

Postoperative bowel complications after non-shunt-related neurosurgical procedures: case series and review of the literature.

Postoperative bowel complications after non-shunt-related neurosurgical procedures are relatively rare. In an effort to identify the primary risk factors, we evaluated postoperative bowel complications in cranial, endovascular, and spinal procedures in neurosurgery patients using our own institutional case series along with a literature review.We identified severe postoperative bowel complications that occurred at our institution after non-shunt-related neurosurgical procedures between July 2016 and December 2018. We also completed a systematic review of PubMed/MEDLINE using search terms related to bowel complications.At our institution, 7 patients (average age 49.7 ± 9.5 years, range 34-60; no apparent sex predilection) had severe postoperative bowel complications after undergoing a total of 10 neurosurgical procedures. Diagnosis was on average 1 week postoperatively (range 5-13 days), and the time between radiographic/clinical diagnosis and either surgery or death was 1.3 ± 1.4 days (range 0-4 days). Bowel perforation occurred in 4 patients. Five of the patients died, 3 as a direct result of the bowel complication. In the literature review, we identified 6487 spine and 66 cranial and/or endovascular bowel complications after neurosurgical procedures.Our case series and literature review demonstrate that severe postoperative bowel complications after non-shunt-related neurosurgical procedures, while rare, carry significant morbidity/mortality despite prompt and aggressive management. These can also happen without direct injury to bowel tissue, instead occurring as sequelae of inflammatory processes, as well as from delayed mobility, extended use of opiate narcotics, and lack of standardized protocols to ensure early bowel movements that likely stems from unfamiliarity with this potentially devastating complication.

Visual and Patient-Reported Outcomes of a Diffractive Trifocal Intraocular Lens Compared with Those of a Monofocal Intraocular Lens.

PURPOSE: To evaluate the effectiveness and safety of a trifocal intraocular lens (IOL), the TFNT00 (Alcon, Fort Worth, TX), versus a monofocal IOL, the SN60AT (Alcon). DESIGN: Food and Drug Administration-approved, prospective, multicenter, nonrandomized, parallel-group, assessor-masked, confirmatory trial. PARTICIPANTS: Patients enrolled were 22 years of age or older with a diagnosis of bilateral cataract with planned removal by phacoemulsification with a clear corneal incision. METHODS: Consented participants selected their preferred IOL, which was implanted sequentially into each eye of patients meeting eligibility criteria. MAIN OUTCOME MEASURES: The coprimary effectiveness outcomes were mean photopic monocular best-corrected distance visual acuity (BCDVA; 4 m) and distance-corrected near visual acuity (DCNVA; 40 cm) at 6 months after surgery. Secondary effectiveness outcomes included mean monocular distance-corrected intermediate visual acuity (DCIVA; 66 cm) and proportion of participants responding "never" to question 1 of the Intraocular Lens Satisfaction questionnaire (regarding frequency of spectacle use in the past 7 days). Safety outcomes included frequency of "severe" and "most bothersome" visual disturbances. RESULTS: Two hundred forty-three patients underwent cataract surgery with bilateral implantation of the TFNT00 (n = 129) or SN60AT (n = 114) and were followed up for 6 months. Noninferiority of TFNT00 to SN60AT in mean photopic monocular BCDVA (95% upper confidence limit of the difference was <0.1 logarithm of the minimum angle of resolution [logMAR] margin), and superiority in mean photopic monocular DCNVA (difference of 0.42 logMAR; P < 0.001) and DCIVA (difference of 0.26 logMAR; P < 0.001) were demonstrated. The proportion of patients never requiring glasses overall was superior for TFNT00 versus SN60AT (80.5% and 8.2%, respectively). Starbursts, halos, and glare were the most frequently rated severe symptoms with TFNT00; however, less than 5% of patients were very bothered at month 6. CONCLUSIONS: The TFNT00 exhibited superior monocular DCNVA and DCIVA to a spherical monofocal IOL, with comparable monocular BCDVA. Binocular visual acuity was 20/25 or better for distance to near (+0.5 D to -2.5 D), resulting in high levels of spectacle independence. Less than 5% of patients were very bothered by the photic visual disturbances associated with the TFNT00 at 6 months after surgery.

Genomic insights into natural selection in the common loon (Gavia immer): evidence for aquatic adaptation.

BACKGROUND: The common loon (Gavia immer) is one of five species that comprise the avian order Gaviiformes. Loons are specialized divers, reaching depths up to 60 m while staying submerged for intervals up to three minutes. In this study we used comparative genomics to investigate the genetic basis of the common loon adaptations to its ecological niche. We used Illumina short read DNA sequence data from a female bird to produce a draft assembly of the common loon (Gavia immer) genome. RESULTS: We identified 14,169 common loon genes, which based on well-resolved avian genomes, represent approximately 80.7% of common loon genes. Evolutionary analyses between common loon and Adelie penguin (Pygoscelis adeliae), red-throated loon (Gavia stellata), chicken (Gallus gallus), northern fulmar (Fulmarus glacialis), and rock pigeon (Columba livia) show 164 positively selected genes in common and red-throated loons. These genes were enriched for a number of protein classes, including those involved in muscle tissue development, immunoglobulin function, hemoglobin iron binding, G-protein coupled receptors, and ATP metabolism. CONCLUSIONS: Signatures of positive selection in these areas suggest the genus Gavia may have adapted for underwater diving by modulating their oxidative and metabolic pathways. While more research is required, these adaptations likely result in (1) compensations in oxygen respiration and energetic metabolism, (2) low-light visual acuity, and (3) elevated solute exchange. This work represents the first effort to understand the genomic adaptations of the common loon as well as other Gavia and may have implications for subsequent studies that target particular genes for loon population genetic, ecological or conservation studies.

Academy IRIS® Registry Analysis of Incidence of Laser Capsulotomy Due to Posterior Capsule Opacification After Intraocular Lens Implantation.

Purpose: Academy IRIS® (Intelligent Research in Sight) Registry was used to determine the incidence of postoperative neodymium-doped yttrium aluminum garnet laser capsulotomy (Nd:YAG) and time to posterior capsular opacification (PCO) diagnosis based on intraocular lens (IOL) type and brand. Methods: This retrospective analysis included eyes implanted with 1 of 2 IOL brands, with ≥365 days of follow-up available in the IRIS Registry, and ≥2 visits within 180 days of surgery. Analyses included Nd:YAG incidence due to PCO within 1 year after surgery by IOL type and brand, mean time to PCO diagnosis, and mean time to Nd:YAG. Results: Of 89,947 eyes after cataract surgery, 24,834 (28%) had PCO diagnosis within 365 days, and 9262 (10%) underwent Nd:YAG; 4.1% of 57,523 eyes with monofocal and 21.2% of 32,424 eyes with diffractive multifocal (MF) or diffractive extended depth of focus (EDOF) IOLs had Nd:YAG. Nd:YAG was 3.2 times more likely in eyes with diffractive MF or diffractive EDOF IOLs versus monofocal. For monofocal IOLs, 3.2% of eyes with AcrySof® and 8.1% of eyes with Tecnis® had Nd:YAG (P<0.0001). For diffractive MF or diffractive EDOF IOLs, 13.0% of eyes with AcrySof and 21.7% of eyes with Tecnis had Nd:YAG (P<0.0001). Nd:YAG risk was 2.4 times higher in eyes with Tecnis versus AcrySof IOLs. Overall, mean time to PCO diagnosis and Nd:YAG was 150.7 and 180.7 days. Mean time to PCO for monofocal versus diffractive MF or diffractive EDOF IOLs was 165.3 versus 139.7 days (P<0.0001). Mean time to Nd:YAG for monofocal versus diffractive MF or diffractive EDOF IOLs was 196.4 versus 175.3 days (P<0.05). Conclusion: Real-world data for AcrySof and Tecnis IOLs revealed lower Nd:YAG rates and longer time to PCO diagnosis and Nd:YAG after monofocal versus diffractive multifocal or diffractive EDOF implantation. Nd:YAG rates were significantly lower with AcrySof versus Tecnis IOLs.

Herpes Simplex Virus Meningoencephalitis Following Pulse-Dose Methylprednisolone: A Case Report and Literature Review.

BACKGROUND Several cases of herpes simplex virus type 1 meningoencephalitis (HSVE) have been reported in patients receiving steroids, but the exact contribution of steroids to the disorder remains unclear because other risk factors, such as chemotherapy, brain radiation, or surgery, were present in almost all cases. CASE REPORT We report the case of a 76-year-old man who developed HSVE following the administration of pulse-dose steroids. The patient had occupational asbestos exposure and a chronic interstitial lung disease of unclear etiology (sarcoidosis versus hypersensitivity pneumonitis) and was admitted for acute-on-chronic respiratory failure requiring mechanical ventilation. After a negative infectious workup and several days of antibiotics without improvement, pulse-dose steroids were administered. In the following days, the patient developed a fever and worsening encephalopathy. A lumbar puncture showed elevated nucleated cells and positive polymerase chain reaction for herpes simplex virus 1 in the cerebrospinal fluid, confirming the diagnosis of HSVE. Acyclovir treatment was initiated, but the patient later died as a result of persistent severe encephalopathy and respiratory failure with an inability to wean mechanical ventilation. CONCLUSIONS Clinicians should keep in mind that HSVE is a potential complication of steroids and carefully consider the benefit/risk ratio of pulse-dose steroids, taking into account associated factors of immunosuppression. A high level of awareness should be especially maintained in critically ill patients because of associated risk factors (critical illness immune paralysis) and because neurological signs of HSVE may be missed in mechanically ventilated, sedated patients.

Angiosarcoma of the Face: A Case Study and Literature Review of Local and Metastatic Angiosarcoma.

Angiosarcomas are vascular malignancies with a tendency to spread extensively both locally and systemically. We report a case of cutaneous angiosarcoma of the face in a 53-year-old man that was originally misdiagnosed as an abscess. Initially small, the lesion enlarged over a four-to-six-month period and began to bleed. Two shave biopsies were performed that returned a diagnosis of angiosarcoma. The patient underwent radical resection and lymph node dissection, which revealed positive margins and ten of forty-six positive lymph nodes. The patient was treated with paclitaxel and concurrent radiation therapy (RT). Restaging scans showed a new sclerotic lesion of the T10 vertebra, three hepatic lesions, and an adrenal lesion, all concerning for metastasis. Biopsy of one of the hepatic lesions was consistent with metastatic angiosarcoma. In this review, we discuss the presentation of cutaneous angiosarcoma, the importance of early diagnosis, and the treatment options available for metastatic disease that has failed first-line chemotherapy.

The AcrySof Toric intraocular lens in subjects with cataracts and corneal astigmatism: a randomized, subject-masked, parallel-group, 1-year study.

PURPOSE: To compare the AcrySof Toric intraocular lens (IOL) and an AcrySof spherical control IOL and to investigate rotational stability of the AcrySof Toric IOL (Alcon Laboratories, Inc., Fort Worth, TX) in subjects with cataracts and preexisting corneal astigmatism. DESIGN: Randomized, subject-masked, parallel-group, multicenter, 1-year study. PARTICIPANTS: We included 517 subjects (Toric IOL, n = 256; control IOL, n = 261). METHODS: Unilateral implantation of an AcrySof Toric or AcrySof spherical control IOL (spherical powers, 12.00-25.00 diopters [D]; cylinder powers 1.50, 2.25, or 3.00 D for corneal astigmatism correction of 0.75 to < 1.50, ≥ 1.50 to <2.00, and ≥ 2.00 D with no upper limit, respectively). No limbal relaxing incisions were permitted. MAIN OUTCOME MEASURES: Visual acuity outcomes, IOL position, patient-reported spectacle use, and safety. RESULTS: One year postoperatively, best spectacle-corrected distance visual acuity of ≥ 20/20 was 77.7% (Toric IOL) versus 69.2% (control IOL). Uncorrected distance visual acuity of 20/20 or better was 40.7% (Toric IOL) versus 19.4% (control IOL; P<0.05). Mean absolute residual refractive cylinder was 0.59 D (Toric IOL) versus 1.22 D (control IOL; P<0.0001). Mean rotation was < 4° (range, 0°-20°) for the Toric IOL. Six-month spectacle freedom was 61.0% (Toric IOL) and 36.4% (control IOL; P < 0.0001). Complications in both groups were few and were as would be expected with cataract surgery. CONCLUSIONS: Favorable efficacy, rotational stability, distance vision spectacle freedom, and safety results support the use of the AcrySof Toric IOL for patients with cataracts and corneal astigmatism. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Physical interaction between replication protein A (RPA) and MRN: involvement of RPA2 phosphorylation and the N-terminus of RPA1.

Replication protein A (RPA) is a heterotrimeric protein consisting of RPA1, RPA2, and RPA3 subunits that binds to single-stranded DNA (ssDNA) with high affinity. The response to replication stress requires the recruitment of RPA and the MRE11-RAD50-NBS1 (MRN) complex. RPA bound to ssDNA stabilizes stalled replication forks by recruiting checkpoint proteins involved in fork stabilization. MRN can bind DNA structures encountered at stalled or collapsed replication forks, such as ssDNA-double-stranded DNA (dsDNA) junctions or breaks, and promote the restart of DNA replication. Here, we demonstrate that RPA2 phosphorylation regulates the assembly of DNA damage-induced RPA and MRN foci. Using purified proteins, we observe a direct interaction between RPA with both NBS1 and MRE11. By utilizing RPA bound to ssDNA, we demonstrate that substituting RPA with phosphorylated RPA or a phosphomimetic weakens the interaction with the MRN complex. Also, the N-terminus of RPA1 is a critical component of the RPA-MRN protein-protein interaction. Deletion of the N-terminal oligonucleotide-oligosaccharide binding fold (OB-fold) of RPA1 abrogates interactions of RPA with MRN and individual proteins of the MRN complex. Further identification of residues critical for MRN binding in the N-terminus of RPA1 shows that substitution of Arg31 and Arg41 with alanines disrupts the RPA-MRN interaction and alters cell cycle progression in response to DNA damage. Thus, the N-terminus of RPA1 and phosphorylation of RPA2 regulate RPA-MRN interactions and are important in the response to DNA damage.

Recognition of cisplatin-DNA interstrand cross-links by replication protein A.

Replication protein A (RPA) is a heterotrimeric protein that is required for DNA replication and most DNA repair pathways. RPA has previously been shown to play a role in recognizing and binding damaged DNA during nucleotide excision repair (NER). RPA has also been suggested to play a role in psoralen DNA interstrand cross-link (ICL) repair, but a clear biochemical activity has yet to be identified in the ICL DNA repair pathways. Using HeLa cell extracts and DNA affinity chromatography, we demonstrate that RPA is preferentially retained on a cisplatin interstrand cross-link (ICL) DNA column compared with undamaged DNA. The retention of RPA on cisplatin intrastrand and ICL containing DNA affinity columns is comparable. In vitro electrophoretic mobility shift assays (EMSAs) using synthetic DNA substrates and purified RPA demonstrate higher affinity for cisplatin ICL DNA binding compared with undamaged DNA. The enhanced binding of RPA to the cisplatin ICL is dependent on the DNA length. As the DNA flanking the cisplatin ICL is increased from 7 to 21 bases, preferential RPA binding is observed. Fluorescence anisotropy reveals greater than 200-fold higher affinity to a cisplatin ICL containing 42-mer DNA compared with an undamaged DNA and a 3-4-fold higher affinity when compared with a cisplatin intrastrand damaged DNA. As the DNA length and stringency of the binding reaction increase, greater preferential binding of RPA to cisplatin ICL DNA is observed. These data are consistent with a role for RPA in the initial recognition and initiation of cisplatin ICL DNA repair.

Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity.

BACKGROUND: Pheochromocytomas are uncommon neuroendocrine tumors of the adrenal medulla. Malignant behavior is seen in approximately 10% of these lesions, evidenced by distant metastasis to sites without chromaffin tissue. Here we report a rare case of intracranial epidural metastases of an adrenal pheochromocytoma in a 24-year-old man. CASE DESCRIPTION: The patient originally presented at age 10 years with adrenal pheochromocytoma and subsequently developed extensive metastatic bone and lung disease. He was monitored in the intervening years until recent imaging demonstrated an enlarging right parietal mass. On surgical resection of the parietal lesion, the tumor was highly vascularized and confined to the epidural space. CONCLUSIONS: To the best of our knowledge, this is the first reported case of metastatic epidural spread of pheochromocytoma without concomitant subdural or intraparenchymal extension.

Breast surgery techniques: preoperative bracketing wire localization by surgeons.

With the development of expertise in image guidance for breast surgery, many surgeons now perform preoperative wire localization themselves. Use of a single wire versus multiple wires to bracket a radiographic breast abnormality has previously been described, although benefits of this technique based on clinical outcomes such as margin status, tissue volume removed, and re-excision rates have not been established. This study is a retrospective analysis of wire-localized breast biopsies performed by 14 surgeons over 29 months; stereotactic and ultrasound guidance were used. During this time, 489 wire localizations were done, of which 159 used multiple wires. Two hundred eleven of these biopsies were done for malignant disease, 86 using multiple wires. After controlling for tumor node metastases stage, single and multiple wire placements were compared using endpoints of margin status, need for re-excision, and total volume of tissue removed. Neither margin status nor re-excision was related to the number of wires placed. However, the number of wires placed was significantly related to the total volume of tissue removed. Use of more than one localizing wire was associated with greater volume of tissue removal (measured in centimeters cubed) in benign disease (46 vs 25, P < 0.001), equivalent volumes in stage 0 disease (73 vs 67), less volume in stage 1 disease (113 vs 164), and less volume in stages 2 through 4 (158 vs 207, P = 0.03). Outcomes based on surgeon case volume during the study period demonstrated that low- (1-40), medium- (41-80), and high-volume (>80) surgeons did not differ in the type or stage of breast pathology treated. Surgeons with high case volumes were more likely to place multiple localizing wires (P < 0.001) and were more likely to do a breast-conserving procedure if re-excision was performed (P < 0.018). Surgeons with low case volumes were more likely to perform a re-excision (P < 0.025). Surgeon experience has a positive impact on quality outcome measures such as performance of a definitive procedure at the time of initial surgery and use of breast-conserving procedures at the time of re-excision. Multiple wire localization can be used to significantly reduce the volume of breast tissue removed in malignant disease without sacrificing margin status or increasing the need for future re-excision.

A case study of right ventricular rupture in an elderly victim of motor vehicle crash: incorporating end-of-life care into trauma nursing.

Cardiac trauma fatalities occur in 22% of victims of motor vehicle crash. Blunt cardiac trauma may result in myocardial rupture. Mechanisms of injury include compression, deceleration, laceration, and "hydraulic ram" effect. Diagnosis is difficult because of coexisting injuries and the lack of evidence-based protocols. Physiological changes in the elderly and the presence of comorbid illness result in poor survival rates when myocardial rupture occurs. Trauma nurses must be prepared to provide end-of-life care related to the poor outcome associated with myocardial rupture. This case study reports a right ventricular rupture in an elderly patient involved in a frontal motor vehicle crash.

A comparison of infusion volumes in the measurement of intra-abdominal pressure.

Bladder pressure measurement through a foley catheter is the current standard in monitoring for intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Accurate pressure transduction requires a continuous fluid column with a small volume of transducing medium at the tip of the catheter. Infusing excessive fluid volume can falsely elevate the measured intra-abdominal pressure (IAP) due to bladder overdistention and can lead to intrinsic muscular contraction. This effect can be seen with volumes as low as 60 mL. Recent expert consensus has recommended 25 mL as the maximal infusion volume; however, 50 mL is the most commonly cited volume of infusion in the literature. The purpose of this analysis was to determine the variance between IAP values using a range of volume infusions between 10 and 60 mL. Eighteen adult, surgical intensive care unit (SICU) patients who were undergoing IAP measurement for IAH or clinically indicated monitoring were enrolled in a prospective, nontreatment study. Intra-abdominal pressure measurements were obtained with stepwise increases of injectate volume from 10 to 60 mL (in 10 mL increments). Bland-Altman analyses and receiver operating characteristic (ROC) curves were used for analysis. After analysis accounting for data correlation within patients, means and standard deviations were generated for differences between 50 mL and 10, 20, 30, 40, and 60 mL bladder infusion volumes. Bland-Altman analyses showed good agreement between measurements and no significant difference in variance (mean < or =1.35 mm Hg) between volume comparisons. The ROC curve generated for each test volume using a diagnostic pressure value for IAH (!12 mm Hg) showed that a value between 11 and 12 mm Hg gave the best combination of sensitivity and specificity for all test volumes. In SICU patients, with a clinical indication for IAP monitoring, bladder infusion volumes between 10 mL and 60 mL provide consistent IAP measurements.

Status of toric intraocular lenses.

PURPOSE OF REVIEW: To provide an update on the status of toric intraocular lenses. These lenses can be used as an alternative or adjunct to corneal astigmatic incisions for correcting preexisting astigmatism in patients with cataracts. They are a particularly attractive option in those cases where limbal-relaxing incisions are not powerful or predictable enough. Other toric lenses may correct astigmatism in addition to spherical refractive errors in phakic patients. RECENT FINDINGS: Toric lenses have continued to gain popularity with the US Food and Drugs Administration (FDA) approval of the Acrysof Toric intraocular lenses. This lens is designed to be implanted in patients undergoing cataract removal and who have significant preexisting corneal astigmatism. In the FDA clinical trial, study patients received one of the three cylindrical powers, and control patients received a standard monofocal intraocular lenses. The study found that the Acrysof Toric intraocular lenses provided excellent visual outcomes and exhibited excellent rotational stability. With the Acrysof Toric intraocular lenses, the average lens rotation was less than 4 degrees from the lens' initial placement at 6 months after surgery. SUMMARY: Toric intraocular lenses provide excellent vision for astigmatic cataract patients, and new designs are significantly improving visual acuity by minimizing the risk of rotation.

Granulocyte-macrophage colony-stimulating factor is a chemoattractant cytokine for human neutrophils: involvement of the ribosomal p70 S6 kinase signaling pathway.

GM-CSF stimulates proliferation of myeloid precursors in bone marrow and primes mature leukocytes for enhanced functionality. We demonstrate that GM-CSF is a powerful chemotactic and chemokinetic agent for human neutrophils. GM-CSF-induced chemotaxis is time dependent and is specifically neutralized with Abs directed to either the ligand itself or its receptor. Maximal chemotactic response was achieved at approximately 7 nM GM-CSF, and the EC(50) was approximately 0.9 nM. Both concentrations are similar to the effective concentrations of IL-8 and less than the effective concentrations of other neutrophil chemoattractants such as neutrophil-activating peptide-78, granulocyte chemotactic protein-2, leukotriene B(4), and FMLP. GM-CSF also acts as a chemoattractant for native cells bearing the GM-CSF receptor, such as monocytes, as well as for GM-CSF receptor-bearing myeloid cell lines, HL60 (promyelomonocyte leukemic cell line) and MPD (myeloproliferative disorder cell line), following differentiation induction. GM-CSF induced a rapid, transient increase in F-actin polymerization and the formation of focal contact rings in neutrophils, which are prerequisites for cell migration. The mechanism of GM-CSF-induced chemotaxis appears to involve the cell signaling molecule, ribosomal p70 S6 kinase (p70S6K). Both p70S6K enzymatic activity and T(421)/S(424) and T(389) phosphorylation are markedly increased with GM-CSF. In addition, the p70S6K inhibitor hamartin transduced into cells as active protein, interfered with GM-CSF-dependent migration, and attenuated p70S6K phosphorylation. These data indicate that GM-CSF exhibits chemotactic functionality and suggest new avenues for the investigation of the molecular basis of chemotaxis as it relates to inflammation and tissue injury.