Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.

BACKGROUND: Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections. METHODS: Thirteen patients were studied at baseline, 3, 5, and 7 days after discontinuation of clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow(®) assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100(®) (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated-measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100 closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank test was used to compare the frequencies of ≥30%, 11-29%, and ≤10% platelet inhibition between the baseline and subsequent sampling points after discontinuation of clopidogrel. RESULTS: On day 3 after clopidogrel discontinuation, two subjects had ≥30%, seven subjects had 11-29%, and four subjects had ≤10% platelet inhibition; the corresponding numbers were 0, 3, and 10 subjects on day 5 (P=0.04). There were no differences between the ≥30%, 11-29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13 subjects, P=1.0). PFA-ADP closure times were normal throughout the study period except in one patient. CONCLUSIONS: These findings support the recommendation that discontinuation of clopidogrel for 5 days allows >70% of platelet function and might be adequate before a neuraxial injection is performed.

Inflammatory bowel disease and pregnancy.

Most women with inflammatory bowel disease who desire to become pregnant can expect to conceive successfully, carry to term, and deliver a healthy infant. However, the management of inflammatory bowel disease during pregnancy remains challenging, and some women with ulcerative colitis or Crohn's disease will have difficulty becoming pregnant or have increased disease symptoms while pregnant. Control of disease activity before conception and during pregnancy is critical to optimize both maternal and fetal health. The natural history of inflammatory bowel disease during pregnancy will be reviewed and the medical and surgical therapy discussed.

Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study.

BACKGROUND: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. AIM: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. METHODS: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed. RESULTS: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). CONCLUSIONS: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

Inspiratory work and airway pressure with continuous positive airway pressure delivery systems.

To determine work-of breathing with continuous positive airway pressure (CPAP) delivery systems, we used a lung model to simulate spontaneous breathing. "Additional work" during tidal breathing was derived by comparing change in airway pressure with change in tidal volume. Seven demand-flow CPAP delivery systems were compared with one continuous-flow, 5-L reservoir-bag system (flow of 60 L/min to maintain positive airway pressure). It was concluded that demand-flow CPAP delivery systems vary widely in the amount of additional work required of a patient. When a lung model is used, some demand-flow systems perform as well as, or better than, a continuous-flow reservoir-bag system.

Pulmonary, chest wall, and lung-thorax elastances in acute respiratory failure.

The usefulness of lung-thorax compliance (or elastance) as an index of pulmonary compliance (or elastance) was examined in 15 patients being ventilated for acute respiratory failure. Mean lung-thorax elastance (ELT) was 27.9 +/- 2.6 cm H2O/L, and the chest wall accounted for 34 +/- 2 percent of the mean total value. Changes in ELT caused by increments of positive end-expiratory pressure correlated only with changes in pulmonary elastance (r = 0.96; P less than 0.001) and not with chest wall elastance, although individual patients varied as to the contribution of the chest wall component. Lung-thorax elastance increased in direct proportion (1:1) to increases in pulmonary elastance, whereas the changes in lung-thorax compliance were only half those in pulmonary compliance. We conclude that elastance is a more useful clinical index than compliance.

Factors affecting perioperative pulmonary function in acute respiratory failure.

To determine the magnitude, duration, and associated factors of perioperative changes in pulmonary function, we retrospectively reviewed the medical records of 145 patients who required preoperative mechanical ventilation for acute respiratory failure before undergoing 200 surgical procedures. Patients were grouped into five pulmonary diagnostic categories: (1) adult respiratory distress syndrome (ARDS) (n = 49); (2) pneumonia (n = 20); (3) atelectasis (n = 65); (4) congestive heart failure (n = 11); and (5) acute ventilatory failure (n = 55). Sixty patients underwent intra-abdominal surgery, 135 patients required surgery on the periphery, and five patients had a thoracotomy. For all patients, PaO2/FIO2 declined significantly from 321 mm Hg (mean) preoperatively to 258 mm Hg intraoperatively, and shunt fraction (Qs/QT) increased from 0.16 to 0.23 without a significant change in PaCO2. The magnitude of the increase in Qs/QT did not differ among pulmonary diagnostic groups. Preoperatively, patients undergoing laparotomy had lower PaO2/FIO2 (278 vs 340) and higher Qs/QT (0.19 vs 0.14) than patients requiring surgery on the periphery. Intraoperatively, Qs/QT increased more during abdominal procedures than during peripheral procedures. Intraoperative hypoxemia (PaO2/FIO2 less than 80 mm Hg) occurred during 13 procedures. Hypoxemic patients had a mean increase in Qs/QT of 0.20 (0.25 preoperatively to 0.45 intraoperatively), and a significant increase in PaCO2 from 38 mm Hg to 45 mm Hg intraoperatively). In general, these patients had ARDS (n = 10), sepsis (n = 10), a laparotomy (n = 9), and intraoperative mechanical ventilation via the Ohio Anesthesia ventilator (n = 8), a commonly used operating room ventilator. Their preoperative peak airway pressure (54 cm H2O) and minute ventilation (20 L/min) requirements exceeded the capabilities of the Ohio Anesthesia ventilator and likely contributed to impaired gas exchange intraoperatively. Within the first several hours postoperatively, PaO2/FIO2 recovered to preoperative levels in all patients, even in those who had severe intraoperative hypoxemia develop and who underwent laparotomy. We conclude that most patients with acute respiratory failure receiving preoperative mechanical ventilation experienced mild-to-moderate deterioration in intraoperative pulmonary oxygen exchange that rapidly returned to preoperative levels after surgery. We recommend that necessary surgery not be postponed by concern that pulmonary function will be worsened by surgery and anesthesia.

Value of C-reactive protein determination in the initial diagnostic evaluation of the febrile, neutropenic child with cancer.

We studied prospectively the value of administration C-reactive protein (CRP) in the diagnostic evaluation of the child with cancer hospitalized for fever and neutropenia. During a 7-month period 74 patients with malignant disease had 122 hospital admissions because of fever and neutropenia. All patients had a serum CRP obtained 8 to 24 hours after the onset of fever as part of their initial evaluation. There was a borderline correlation between serum CRP concentration and temperature at admission (P = 0.06). Patients with fever without an identifiable source had significantly lower CRP concentrations compared with those having focal or microbiologically documented infection (34.9 +/- 6 vs. 70.2 +/- 12 mg/liter; P = 0.0005). Twelve patients had positive blood cultures, 5 of which were coagulase-negative staphylococci considered to be central venous catheter-related infection or colonization. CRP concentrations were significantly lower in these 5 patients compared with the 7 patients with septicemia caused by other organisms (21 +/- 9 vs. 113 +/- 23 mg/liter; P = 0.01). In distinguishing between septicemic and nonsepticemic children, serum CRP was found to have excellent sensitivity and negative predictive value at concentration limits of 20, 50 and 100 mg/liter. However, both specificity and positive predictive value were low at these respective levels, thus limiting the overall utility of serum CRP in the initial empiric management of the febrile, neutropenic child with cancer.

The influence of human endotoxemia on CD95-induced apoptosis.

BACKGROUND: The responses of monocyte and neutrophil tumor necrosis factor receptor type 1 (TNFR-1) and TNFR-2 during systemic inflammation have been described previously. Several other members of the TNFR superfamily also appear to have regulatory roles in immunocyte function, including apoptosis. However, the response of these other receptor members, such as CD95, to systemic inflammation is unclear. OBJECTIVES: To compare the response of CD95 with that of TNFR during systemic inflammation and to assess the influence of the inflammatory milieu on CD95 function. SETTING: Adult clinical research center of a university hospital. SUBJECTS AND METHODS: Five healthy male subjects were administered intravenous endotoxin (2 ng/kg), and systemic response was measured by cytokine analysis and receptor expression assays during a 48-hour period. CD95 function during systemic inflammation was assessed using a Jurkat cell bioassay for degree of apoptosis. RESULTS: Monocyte and neutrophil CD95 expression exhibited changes parallel to that of TNFR following endotoxin injection. In contrast to soluble TNFR, which was transiently elevated during endotoxemia, soluble CD95 levels remained unchanged from baseline. Jurkat cells incubated in normal and post-endotoxin serum samples equally exhibited less than 10% spontaneous apoptosis. No soluble CD95 ligand was detectable in experimental human endotoxemia. CONCLUSIONS: Cell-associated CD95 exhibited changes parallel to its receptor family member TNFR following endotoxin administration. Soluble CD95 is present in human serum samples, but the levels remained unchanged following endotoxin administration. No soluble CD95 ligand activity was detectable by enzyme-linked immunosorbent assay or by functional assay. The potential protective role of soluble CD95 in human serum samples against CD95 ligand-induced apoptosis remains to be defined.

Cytogenetic features of childhood acute lymphoblastic leukemia. A concordance study and a Pediatric Oncology Group study.

Cytogenetic analysis yields important objective information that has been shown to correlate with both patient response to therapeutic intervention and patient survival. Bone marrow samples are submitted to a common reference laboratory for cytogenetic analysis from children with newly diagnosed acute lymphoblastic leukemia (ALL) registered on frontline Pediatric Oncology Group (POG) therapeutic studies (classification 8600 series). A portion of the sample from the Texas Children's Hospital (Houston, TX) a POG affiliate, was also submitted to a local cytogenetics laboratory for analysis. This study retrospectively compares karyotypic data and methods from the Laboratory of Medical Genetics, University of Alabama at Birmingham (reference laboratory) with those of the Kleberg Cytogenetics Laboratory at the Baylor College of Medicine (local laboratory) over a 35-month period to evaluate the effect of differences in specimen procurement, handling, and laboratory methodology on yield of cytogenetic information. Each laboratory was able to identify clonal abnormalities in 72% of cases examined during the last year of the study. When these data were combined, the overall detection rate of clonal abnormalities was 87.5%. Utilizing the same bone marrow aspirate from 73 children, this study demonstrates that cytogenetic methodology significantly affects the yield of identifiable clonal abnormalities, while variables such as overnight shipping have no discernable effect. This study also supports the contention that central laboratory testing effectively yields information critical to ongoing large-scale research endeavors.

Differential expression of MAG, MBP and L1 in the developing lateral superior olive.

The aim of this study was to investigate whether glial-associated molecules exhibit a pattern of expression that could influence oriented dendrite outgrowth in the gerbil lateral superior olive (LSO). In particular, we have previously noted that axon fascicles are oriented parallel to isofrequency laminae in the medial limb of the LSO, as are LSO dendrites, a phenotype that emerges postnatally. Therefore, we examined the immunocytochemical staining pattern of antibodies directed against three proteins that are found along axons: myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and neuron-glia cell adhesion molecule (L1). MAG staining was first observed at postnatal day (P) 4 on the axon fibers surrounding the LSO. By P7 there was a differential pattern of MAG staining within the LSO, and immunopositive fibers were observed solely in the medial limb (e.g., high frequency projection region). Between P7 and P12, MAG staining was restricted largely to fascicles in the medial limb, and these were oriented parallel to the isofrequency axes. Few positive fibers of irregular orientation were observed in the lateral limb (e.g., low frequency projection region). Significant MAG-staining was not observed in the lateral limb until P15. The MAG immunoreactivity extended throughout the LSO by P21, although it was no longer restricted to axon fascicles. In contrast, MBP-positive fibers were uniformly distributed within the LSO by P12. Finally, L1 was found on oriented axon fascicles at P0, but became sparsely distributed throughout the LSO neuropil after P7, and was restricted to neuron cell bodies in the adult. Taken together, the results suggest that oriented axon fascicles bearing MAG and L1 may contribute to the developmental refinement of dendrite and axon arbors within the LSO.

Measuring intra-esophageal pressure to assess transmural pulmonary arterial occlusion pressure in patients with acute lung injury: a case series and review.

BACKGROUND: Positive end-expiratory pressure (PEEP) may interfere with accurate assessment of cardiac function. PEEP may decrease left ventricular volume by lowering the transmural gradient between ventricular and pleural surface pressure (P(PL)) around the heart while raising the absolute pulmonary arterial occlusion pressure (PAOP). Clinical formulas used to predict the transmural PAOP (PAOP(TM)) require subtracting 25-50% of the PEEP level from the PAOP. However, both PAOP and P(PL) are influenced by transmitted PEEP and transmitted intra-abdominal pressure (IAP). We compared PAOP(TM) calculated by measuring intra-esophageal pressure (P(ES)) with PAOP(TM) estimated by clinical formulas. METHODS: Twenty-two P(ES) measurements were made with a bedside pulmonary mechanics monitor (BICORE CP-100) on 11 patients with acute lung injury who had an elevated PAOP (mean +/- standard deviation) of 21.1 +/- 6.2 mm Hg and PEEP of 13.0 +/- 3.8 mm Hg. Paired comparisons were made with the Wilcoxon signed-rank test and multiple comparisons were made using one-way analysis of variance (ANOVA) and the Student-Newman-Keuls test. Pearson product-moment correlation coefficients were calculated. A MEDLINE literature search was done to survey the reported range of PEEP transmitted to P(PL). RESULTS: P(ES) (14.6 +/- 5.0 mm Hg) exceeded PEEP; 9 of 11 patients had clinical evidence of increased IAP. PAOP(TM) predicted by clinical formulas were 13.5-17.7 mm Hg, whereas PAOP(TM) calculated by P(ES) was 6.2 +/- 3.6 mm Hg (p < 0.05). Linear regression revealed a moderate correlation between PAOP and PEEP (r = 0.49, p = 0.02). In contrast, there was a strong correlation between PAOP and P(ES) (r = 0.83, p < 0.0001). A review of data derived from the literature did not show a consistent pattern of PEEP transmission. CONCLUSION: PAOP(TM) calculated by P(ES) may reflect transmitted IAP to the pleural surface. Using P(ES) to calculate PAOP(TM) may provide a more accurate assessment of hemodynamic status than predicting PAOP(TM) using clinical formulas based solely on estimated PEEP transmission.

Lung collapse during low tidal volume ventilation in acute respiratory distress syndrome.

BACKGROUND: Current ventilator management for acute respiratory distress syndrome (ARDS) incorporates low tidal volume (V(T)) ventilation in order to limit ventilator-induced lung injury. Low V(T) ventilation in supine patients, without the use of intermittent hyperinflations, may cause small airway closure, progressive atelectasis, and secretion retention. Use of high positive end-expiratory pressure (PEEP) levels with low V(T) ventilation may not counter this effect, because regional differences in intra-abdominal hydrostatic pressure may diminish the volume-stabilizing effects of PEEP. CASE SUMMARY: A 35-year-old man with abdominal compartment syndrome (intra-abdominal pressure > 48 cm H2O developed ARDS and was treated with V(T) of 4.5 mL/kg and PEEP of 20 cm H2O. Despite aggressive fluid therapy, appropriate airway humidification and tracheal suctioning, the patient developed complete bronchial obstruction, involving the entire right lung and left upper lobe. After bronchoscopy the patient was placed on a higher V(T) (7.0 mL/kg). Intermittent PEEP was instituted at 30 cm H2O for 2 breaths every 3 minutes. This intermittently raised the end-inspiratory plateau pressure from 38 cm H2O to 50 cm H2O. With the same airway humidity and tracheal suctioning practices bronchial obstruction did not reoccur. CONCLUSION: Low V(T) ventilation in ARDS may increase the risk of small airway closure and retained secretions. This adverse effect highlights the importance of pulmonary hygiene measures in ARDS during lung-protective ventilation.

Design and evaluation of a sensory feedback system that provides grasping pressure in a myoelectric hand.

Providing accurate sensory information to the individual with a myoelectric limb is of great importance for improving device use in a wide variety of tasks. A number of feedback systems presently being investigated rely on either vibrotactile or electrotactile skin stimulation, which does not provide sensory patterns similar to those in a natural grasping hand. A prototype system was developed to enhance sensory information transfer by using a technique in which the feedback modality (pressure) was the same as the grasping pressure. The present study compared the developed system (pressure) with vibrotactile feedback, vision, and compounds of these three modes. It was found that the pressure-pressure concept reduced grasping pressure replication errors and error variability.

Nausea and vomiting following thyroid and parathyroid surgery.

STUDY OBJECTIVES: To determine the incidence of postoperative nausea and vomiting (PONV) following thyroid and parathyroid surgery. To determine whether PONV is reduced when propofol is used for maintenance of anesthesia as compared to isoflurane and to evaluate the costs and resource consumption associated with these two anesthetic regimens. DESIGN: Randomized, prospective study. SETTING: University-affiliated hospital--a referral center for endocrinologic surgery. PATIENTS: 118 ASA physical status I and II patients, aged 18 years and older, undergoing elective thyroid or parathyroid surgery. INTERVENTIONS: Patients received either isoflurane (0.5 to 1.3% end-tidal) or propofol (50 to 200 micrograms/kg/min) for maintenance of anesthesia. All patients received propofol for induction of anesthesia, succinylcholine or vecuronium, nitrous oxide, and fentanyl. Prophylactic antiemetics were not administered. Postoperative pain was treated with ketorolac, fentanyl, or acetaminophen. MEASUREMENTS AND MAIN RESULTS: Signs and symptoms of nausea and vomiting were graded on a four point scale as 1 = no nausea; 2 = mild nausea; 3 = severe nausea; 4 = retching and/or vomiting. Grades 3 and 4 were grouped together as PONV. The combined incidence of PONV was 54% over the 24-hour postoperative evaluation period. PONV was significantly more common in patients receiving isoflurane than propofol for maintenance of anesthesia (64% vs. 44%). In women (n = 87), the incidence of PONV was significantly greater in those patients who received isoflurane than those who received propofol for maintenance (71% vs. 42%). However, in men (n = 31), there was no significant difference in PONV between anesthetic regimens (47% with isoflurane vs. 50% with propofol). There were no differences in the duration of stay in the postanesthesia care unit, time to discharge from the hospital, or local wound complications (hematomas) between groups. The use of propofol for maintenance of anesthesia was associated with an additional cost, relative to the isoflurane group, of $54.26 per patient. CONCLUSION: Patients undergoing thyroid or parathyroid surgery are at high risk for the development of PONV. Propofol for maintenance of anesthesia, although more expensive than isoflurane, reduces the rate of PONV in women.

Improved flow and pressure capabilities of the Datex-Ohmeda SmartVent anesthesia ventilator.

STUDY OBJECTIVE: To compare the flow and pressure capabilities of the Datex-Ohmeda SmartVent (Ohmeda 7900, Datex-Ohmeda, Madison, WI) to previous Ohmeda (7810 and 7000, Datex-Ohmeda, Madison, WI) anesthesia ventilators. To determine airway pressure and minute ventilation thresholds for intraoperative use of a critical care ventilator. DESIGN: Three anesthesia ventilators and one critical care ventilator (Siemens Servo 900C, Siemens, Solna, Sweden) were studied in a lung model. Retrospective medical record review. SETTING: Research Laboratory and Critical Care Unit of a Level I Trauma Center. PATIENTS: 145 mechanically ventilated patients treated for acute respiratory failure who underwent 200 surgical procedures. INTERVENTIONS: The effect of increasing pressure on mean inspiratory flow was determined by cycling each ventilator through increasing restrictors. Maximum minute ventilation was measured at low compliance (10-30 mL/cm H2O), positive end-expiratory pressure (PEEP) (0-20 cm H2O), and increased airway resistance (approximately 19 and approximately 36 cm H2O/L/sec) in a mechanical lung model. MEASUREMENTS AND MAIN RESULTS: Flow, volume, and pressure were measured with a pulmonary mechanics monitor (BICORE CP-100, Thermo Respiratory Group, Yorba Linda, CA). Preoperative peak airway pressure and minute ventilation (VE) were extracted from the medical record. Mean inspiratory flow declined with increasing pressure in all anesthesia ventilators. The SmartVent and the 7810 produced greater mean inspiratory flow than did the 7000 ventilator. As compliance progressively decreased, the Siemens, the SmartVent, and the 7810 ventilators maintained VE compared to the 7000 ventilator. The Siemens and the SmartVent maintained VE with PEEP, compared to the 7810 and 7000 ventilators. During increased airway resistance, maximal VE was lower for all ventilators. The SmartVent met the ventilation requirements in 90% of the patients compared to 67% of patients with the 7000 ventilator. CONCLUSION: The improved pressure and flow capabilities of the SmartVent increase the threshold for using a critical care ventilator intraoperatively to a peak airway pressure > 65 cm H2O and/or VE > 18 L/min.

The effects of azidothymidine therapy on pseudocholinesterase concentrations in asymptomatic HIV-positive patients.

The purpose of this study was to determine if a correlation exists between long-term azidothymidine (AZT) therapy and low pseudocholinesterase concentrations in patients who are infected with the human immunodeficiency virus (HIV). A pilot study was conducted of 10 patients infected with HIV, 5 of whom were receiving AZT. Laboratory tests, including complete blood count (CBC), liver function tests, helper/inducer T lymphocyte numbers (CD4), serum dibucaine numbers, and serum pseudocholinesterase concentrations were examined. Control and study subjects both exhibited normal dibucaine numbers, but the pseudocholinesterase concentrations were significantly lower in the group that was not receiving AZT relative to the AZT treatment group. However, only two patients, neither of whom were receiving AZT, demonstrated low or borderline low pseudocholinesterase concentrations according to laboratory criteria. It is possible that pseudocholinesterase synthesis is significantly inhibited by the HIV disease process and that treatment with AZT partly reverses the inhibition. Associated variables contributing to low pseudocholinesterase concentrations in the HIV-positive patient are explored.

Incidence of childhood and adolescent cancer in Texas.

Population-based data from the Texas Cancer Registry were used to describe the incidence of cancer in 1990 among Texas residents younger than 20 years. A total of 788 primary malignant neoplasms were diagnosed. Higher incidence of all cancers was observed among Texas Anglo children compared with Hispanics or African-Americans, and lower rates of central nervous system (CNS) neoplasms were seen among Hispanics. Compared with national data, significantly fewer cases of all cancers combined, non-Hodgkin's lymphoma, neuroblastoma, and CNS neoplasms were seen in Texas Hispanics. The overall incidence of leukemia and acute nonlymphocytic leukemia (ANLL) was highest in Hispanics compared with other Texas children, and a three-fold statistically significant excess of ANLL was evident in Hispanic females compared with national whites. In summary, the incidence of cancer in Texas Hispanic children and adolescents differs from that seen in other racial and ethnic groups. Incidence data for Texas provide additional insight into the descriptive nature of childhood and adolescent cancers.