Prefrontal gamma oscillations reflect ongoing pain intensity in chronic back pain patients

Chronic pain is a major health care issue characterized by ongoing pain and a variety of sensory, cognitive, and affective abnormalities. The neural basis of chronic pain is still not completely understood. Previous work has implicated prefrontal brain areas in chronic pain. Furthermore, prefrontal neuronal oscillations at gamma frequencies (60–90 Hz) have been shown to reflect the perceived intensity of longer lasting experimental pain in healthy human participants. In contrast, noxious stimulus intensity has been related to alpha (8–13 Hz) and beta (14–29 Hz) oscillations in sensorimotor areas. However, it is not fully understood how the intensity of ongoing pain as the key symptom of chronic pain is represented in the human brain. Here, we asked 31 chronic back pain patients to continuously rate their ongoing pain while simultaneously recording electroencephalography (EEG). Time–frequency analyses revealed a positive association between ongoing pain intensity and prefrontal beta and gamma oscillations. No association was found between pain and alpha or beta oscillations in sensorimotor areas. These findings indicate that ongoing pain as the key symptom of chronic pain is reflected by neuronal oscillations implicated in the subjective perception of longer lasting pain rather than by neuronal oscillations related to the processing of objective nociceptive input. The findings, thus, support a dissociation of pain intensity from nociceptive processing in chronic back pain patients. Furthermore, although possible confounds by muscle activity have to be taken into account, they might be useful for defining a neurophysiological marker of ongoing pain in the human brain.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.     

Institutional review of free TRAM flap breast reconstruction

INTRODUCTION: A 10-year experience with breast reconstruction in a university hospital was recently reviewed. The purpose of this study was to determine the subtypes of breast reconstructive procedures and to evaluate the frequency and change in technique over time of free TRAM (transverse rectus abdominis muscle) flap breast reconstruction performed at one institution. Trends in the development of the procedure over this period were also reviewed. MATERIALS & METHODS: Between November 1994 and September 2004, a 10-year retrospective chart review was conducted. The indications for mastectomy and reconstruction were determined. The median age was 48 (range 31-66). The range of follow-up was 2 to 71 months, with a median of 19.5 months. The mean follow-up was 23.5 months. Outcome data were grouped into 2 consecutive 5-year periods (period 1: 1994-1998; period 2: 1999-2004) and evaluated for changes over time in techniques and outcome. Statistical analysis (Decision Analyst, Inc., STATS Statistics software, version 1.1, 1998) was performed using the difference between 2 proportions module to assess the probability of a significant difference in the data for period 1 and period 2 parameters. RESULTS: Over a 10-year period, 117 patients underwent breast reconstruction. This consisted of 12 pedicle procedures (11.3%), including 1 bipedicle flap (0.9%) and 2 bilateral pedicle procedures (1.8%). There were 3 latissimus dorsi pedicle flaps (2.8%). Sixteen patients (15.1%) received tissue expander or implant reconstructions. Of the 117 patients, 79 underwent free flap breast reconstruction. Of the 79 free-flap patients, 22 (27.8%) had bilateral procedures, for a total of 101 free flaps performed in these 79 patients. Fifty-two patients underwent immediate reconstruction (65.8%) and 25 were delayed (31.6%) reconstructions using either deep inferior epigastric artery perforator (DIEP) flaps (4 = 3.9%) or free TRAM flaps (97 = 96.0%). A muscle-sparing technique was used in 43 of the 97 free TRAM flaps (44.3%). The preferred vascular inflow was the internal mammary artery, which was used in 66 out of 101 flaps (65.3%). The rate of anastomotic revision (arterial and venous) was 4.9%. The majority of cases used a 2.5-mm venous coupler (65.3%). In 2 of the free TRAM cases, there was insufficient volume to establish the patients preexisting volume. Therefore, at the patient's request, immediate implants were used to augment the reconstruction. The average hospital stay was 8.13 days, and the average intensive care stay was 4.59 days. When assessed for trends over time, we noted a reduction in our hospital length of stay and our ICU length of stay. CONCLUSION: The experience with free tissue breast reconstruction reveals predominant use of the TRAM flap. This is justified by the reliability of this flap and the advances in achieving esthetic breast reconstruction. Additionally, we have begun performing DIEP free-flap reconstructions. Our clinical practice has evolved concurrent with standards of care, as noted by the increase in use of muscle-sparing techniques and the reduction in the use of dextran. We do not routinely use therapeutic anticoagulation in our cases. Our hospital length of stay and average intensive care length of stay have also decreased over time, consistent with a system-wide effort to increase the efficiency of healthcare delivery.     

Calf stretching in non-weight bearing versus weight bearing

Limited ankle dorsiflexion passive range of motion (DF PROM) has been associated with lower extremity overuse injuries. Therefore, clinicians often prescribe stretching exercises to increase ankle DF PROM. However, there is limited evidence to indicate if any particular gastrocnemius stretching exercise results in greater improvement in DF PROM. The aim of this study was to determine if gastrocnemius stretching in non-weight bearing (NWB) or weight bearing (WB) results in a greater increase of ankle DF PROM. 28 healthy volunteers, aged 18-55 years, who exhibited less than 10 degrees of ankle DF PROM completed the study. Participants were randomized into 2 stretching groups: NWB and WB. Both groups completed a 3-week home gastrocnemius stretching program, consisting of 5 repetitions held for 30 s each, 2 times daily. Participants' ankle DF PROM was measured with a blinded standard goniometer in NWB and WB positions before and after participation in a 3-week home gastrocnemius stretching program. Two 3-way mixed model ANOVAs demonstrated no significant difference in ankle DF PROM between the NWB and WB groups for either the NWB measurement condition (p=0.49) or WB measurement condition (p=0.86). Gastrocnemius stretching exercises performed in NWB or WB were equally effective in increasing ankle DF PROM.     

Frozen section evaluation of cervical conization specimens

Frozen section evaluation was done on 96 conization specimens. One patient had invasive carcinoma, which was correctly diagnosed on frozen section. No patient received inappropriate therapy on the basis of an erroneous diagnosis made from the evaluation of frozen sections. The mean time from initiation of surgery to the surgeon's receipt of the frozen section diagnosis was 0.9 hours. There was no significant increase in the blood loss or intraoperative complication rate when frozen conization was added to either abdominal or vaginal hysterectomy.     

Bleomycin, vincristine, and methotrexate with citrovorum factor rescue in the treatment of advanced squamous cell carcinoma of the cervix

Fourteen patients with advanced or locally recurrent squamous cell carcinoma of the uterine cervix were treated with bleomycin, vincristine, and moderately high dose methotrexate with citrovorum rescue. Two patients (14%) had a partial response; no patient had a complete response. Two patients were felt to have significant bleomycin associated pulmonary toxicity. This chemotherapy regimen is not felt to be clinically useful in our patient population.     

Assessment of the intrarater and interrater reliability of an established clinical task analysis methodology

BACKGROUND: Task analysis may be useful for assessing how anesthesiologists alter their behavior in response to different clinical situations. In this study, the authors examined the intraobserver and interobserver reliability of an established task analysis methodology. METHODS: During 20 routine anesthetic procedures, a trained observer sat in the operating room and categorized in real-time the anesthetist's activities into 38 task categories. Two weeks later, the same observer performed task analysis from videotapes obtained intraoperatively. A different observer performed task analysis from the videotapes on two separate occasions. Data were analyzed for percent of time spent on each task category, average task duration, and number of task occurrences. Rater reliability and agreement were assessed using intraclass correlation coefficients. RESULTS: Intrarater reliability was generally good for categorization of percent time on task and task occurrence (mean intraclass correlation coefficients of 0.84-0.97). There was a comparably high concordance between real-time and video analyses. Interrater reliability was generally good for percent time and task occurrence measurements. However, the interrater reliability of the task duration metric was unsatisfactory, primarily because of the technique used to capture multitasking. CONCLUSIONS: A task analysis technique used in anesthesia research for several decades showed good intrarater reliability. Off-line analysis of videotapes is a viable alternative to real-time data collection. Acceptable interrater reliability requires the use of strict task definitions, sophisticated software, and rigorous observer training. New techniques must be developed to more accurately capture multitasking. Substantial effort is required to conduct task analyses that will have sufficient reliability for purposes of research or clinical evaluation.     

Young age as an adverse prognostic factor in premenopausal women with operable breast cancer

Data regarding young age as an independent prognostic factor have been conflicting. We investigated this variable in 696 premenopausal Vietnamese and Chinese women with operable breast cancer who participated in a clinical trial of adjuvant surgical oophorectomy and tamoxifen. Tumor size and axillary lymph node status did not vary with age. Women < 35 years had a greater fraction of histologic grade III tumors (P = 0.06), and in the two thirds of patients with available data, in women < 35 years, there was a lower percentage of estrogen- and progesterone receptor-positive tumors and a higher percentage of HER2/neu-positive tumors (P > 0.14 for each group). In univariate analyses, compared to women > or = 45 years, women < 35 years and 35-39 years were at greater risk for death (P = 0.002 and P = 0.023, respectively), and compared to women > or = 40, women < 40 were at greater risk of death (P = 0.002). Multivariate analyses supported a conclusion that younger age was an independent adverse prognostic factor for survival (P = 0.005, age as a continuous variable). Kaplan-Meier analyses in all patients and in oophorectomy and tamoxifen-treated patients, but not in observation-only patients, showed statistically significant poorer disease-free and overall survival in women < 40 years compared to those > or = 40 years. Thus, despite efficacy of the combined adjuvant hormonal therapy, younger age was a risk factor for poorer survival.