Sarcomatoid squamous cell carcinoma of the vulva.
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Aged↗
Biomedical subjects
W A Cooper
Publications and source records attributed to W A Cooper.
1H NMR visible lipids are induced by phosphonium salts and 5-fluorouracil in human breast cancer cells.
Cationic lipophilic phosphonium salts (CLPS) selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. The effects of the CLPS p-(triphenylphosphoniummethyl) benzaldehyde chloride (drug A), and [4-(hydrazinocarboxy)-1-butyl] tris-(4-dimethylaminophenyl) phosphonium chloride (drug B), on human breast cells of differing biological properties were assessed using growth inhibition assays and 1H NMR. Drug A and, to a lesser extent, drug B demonstrated selective growth inhibition of the highly tumorigenic DU4475 breast carcinoma cell line compared to the transformed HBL-100 human breast cell line. However, in contrast to previous studies using other cell lines, no synergistic activity was found when the drugs were used in combination. 1H NMR demonstrated significant increases in mobile lipid acyl chain resonances in both cell lines treated with cytotoxic doses (IC50, 48 h) of the drugs used either alone or in combination. Two-dimensional NMR revealed accompanying decreases in phosphocholine/Lys levels in HBL-100 cells treated with A, B, or a 1:1 combination A+B at the IC50, and in DU4475 cells treated with drug A (IC50). This was accompanied by significant increases in cho/Lys ratios with IC50 A or combination A+B treatment. Similar spectra were observed in cells treated with 5-fluorouracil but not methotrexate, indicating that mobile lipid accumulation is a general but not universal response to cytotoxic insult.
Antineoplastic Agents↗
In vivo hemodynamic, histologic, and antimineralization characteristics of the Mosaic bioprosthesis.
BACKGROUND: Performance of bioprosthetic valves is limited by tissue degeneration due to calcification with reduced performance and longevity. The Mosaic bioprosthetic valve (Medtronic Heart Valves, Inc, Minneapolis, MN) combines zero pressure fixation, antimineralization properties of alpha-amino oleic acid (AOA), and a proven stent design. We tested the hypothesis that AOA treatment of Mosaic valves improves hemodynamics, antimineralization properties, and survival in a chronic ovine model. METHODS: Mitral valves were implanted in juvenile sheep with Mosaic valves with AOA treatment (n = 8) or without AOA treatment (non-AOA, n = 8), or Hancock I (HAN, n = 4) tissue valves, and explanted at 20 postoperative weeks. RESULTS: Survival was equivalent in AOA and non-AOA (140 +/- 0.4 and 129 +/- 30 days), but was significantly less in HAN (82 +/- 35). Leaflet calcium (microgCa/mg tissue) was less in AOA (9.6 +/- 13.9; p < 0.05 versus non-AOA and HAN) than non-AOA (96.3 +/- 63.8) and HAN (130.8 +/- 43.2). Explant valve orifice area (cm2) was significantly preserved in the AOA group compared with the non-AOA group (1.5 +/- 0.7 vs 0.8 +/- 0.3; p < 0.05 versus non-AOA and HAN). CONCLUSIONS: We conclude that AOA treatment of Mosaic valves reduces leaflet calcification and valve gradient in juvenile sheep, and that the Mosaic design and fixation features may offer survival advantages that must be confirmed in extended trials.
Animals↗
Management of bronchopleural fistula after lobectomy.
Bronchopleural fistula after lobectomy is fortunately a rare complication. In years past, this complication was encountered far more frequently. However, the morbidity associated with this complication is still significant. Bronchopleural fistulas develop in patients who are at increased risk of surgical morbidity because of their concomitant medical problems or as a result of chemotherapy for lung cancer or immunosuppression in transplant patients. These patients often present in a moribund, septic state, making their treatment even more difficult. Nevertheless, evaluation and management of these patients should proceed in a logical stepwise fashion. Evaluation of the patient with a bronchopleural fistula should proceed in a logical, stepwise manner form diagnosis to pulmonary rehabilitation.
Bronchial Fistula↗
The surgical spectrum of pulmonary neuroendocrine neoplasms.
OBJECTIVES: The purpose of this study is to review our experience with the spectrum of neuroendocrine neoplasms of the lung with emphasis on the histopathologic classification and surgical therapy of each class of neoplasm. DESIGN: This retrospective review covers the entire spectrum of neuroendocrine neoplasms of the lung over an 11-year period (January 1985 to December 1995) in a university hospital setting. Only patients who underwent surgical resection were included in this review. PATIENTS: During this period, a total of 77 patients underwent lung resection for the following neuroendocrine neoplasms: typical carcinoid (TC), 50 patients; atypical carcinoid (AC), 5 patients; large cell neuroendocrine carcinoma (LCNEC), 9 patients; mixed large-small cell neuroendocrine carcinoma (LSNEC), 4 patients; or small cell neuroendocrine carcinoma (SCC), 9 patients. There were 37 men (48.1%) and 40 women (51.9%) among the patients, with a mean age of 57.9 years (range, 14 to 87 years). INTERVENTIONS: Primary surgical resection consisted of the following procedures: 52 lobectomies (67.5%); 10 pneumonectomies (13%); 13 limited resections (16.9%); 1 left main bronchus sleeve resection; and 1 carinal resection. Six patients had the following concomitant procedures: pericardiectomy, 2 patients; mediastinoscopy, 1 patient; chest wall resection, 1 patient; stapling blebs, 1 patient; and transdiaphragmatic liver biopsy, 1 patient. Four patients underwent bilobectomies, and two patients underwent multiple wedge resections. RESULTS: The hospital mortality rate was 2.6% (2 of 77 patients), and both patients died of pulmonary failure. Follow-up was obtained in 62 of 77 patients (80.9%) for an average of 38.1 months (range, 2 to 132 months). There were a total of 13 deaths, and 8 were disease-related (LCNEC, 4 deaths; SCC, 2 deaths; LSNEC, 1 death; and AC tumor, 1 death. The mean disease-free intervals for patients with these neoplasms were the following: TC tumor, 41.3 months; AC tumor, 20 months; LCNEC, 20.4 months; LSNEC, 25 months; and SCC, 48 months. The overall 3-year survival rate was 45.2% (28 of 62 patients). CONCLUSION: This report will emphasize the classification, surgical management, and treatment considerations of pulmonary neuroendocrine neoplasms. Despite the poor overall prognosis in high-grade neuroendocrine tumors of the lung, surgery remains a viable adjunct in the early stages of this disease.
Adolescent↗
Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.
BACKGROUND: Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. METHODS: Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. RESULTS: In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). CONCLUSIONS: DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.
Animals↗
Latency alterations of the auditory brainstem response in audiogenic seizure-prone Long-Evans rats.
Audiogenic seizure susceptibility in the normally seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for audiogenic seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4-6 months, vertex recordings of ABR waves Ia-VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia-V and III-V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.
Acoustic Stimulation↗
Penetrating cardiac trauma at an urban trauma center: a 22-year perspective.
This is a report of a 22-year experience with penetrating cardiac trauma at a single urban Level I trauma center. We conducted a retrospective chart review supplemented by computerized patient log. Comparisons of mortality between Period 1 (1975-1985; 113 patients) and Period 2 (1986-1996; 79 patients) were by chi2 or Fisher's exact tests. Statistical significance was defined as P < or = 0.05. From 1975 to 1996, 192 patients (mean age, 32 years; 88% male) with penetrating cardiac stab wounds (68%) or gunshot wounds (32%) were treated. The most common initial clinical presentation was cardiac tamponade, and most patients (54%) were hypotensive (systolic blood pressure 30-90 mm Hg). The most common initial intervention in the emergency center was tube thoracostomy. The use of pericardiocentesis as a diagnostic and therapeutic modality in the emergency center virtually disappeared in Period 2, as compared with Period 1. Since 1994, surgeon-performed cardiac ultrasound has been performed and has correctly diagnosed hemopericardium in 12 patients (100% survival). The overall mortality for all patients during the 22-year study interval was 25 per cent and was not significantly different between Period 1 (27%) and Period 2 (22%). The mortality associated with gunshot wounds was increased compared with that of stab wounds. Similarly, mortality for patients who arrested in the emergency center was increased compared with those patients who did not arrest. We conclude: 1) cardiac tamponade is the most common presentation in patients with cardiac wounds; 2) pericardiocentesis in the emergency center has essentially disappeared; 3) surgeon-performed ultrasound of the pericardium should improve survival of future patients who are normotensive or mildly hypotensive; 4) over the last 11 years, there has been a substantial decrease in mortality in patients with stab wounds and a statistically significant decrease in arrested patients; and 5) overall mortality for penetrating cardiac trauma has not changed during the 22-year interval.
Adolescent↗
As originally published in 1989: Esophageal carcinoma: surgery without preoperative adjuvant chemotherapy. Updated in 1998.
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Carcinoma↗
Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies.
BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.
Anti-Inflammatory Agents, Non-Steroidal↗
Validation of surgeon-performed emergency abdominal ultrasonography in pediatric trauma patients.
BACKGROUND/PURPOSE: The focused assessment for the sonographic evaluation of trauma patients (FAST) in adults is effective in detecting intraperitoneal and intrapericardial fluid and can be performed quickly by surgeons in the emergency department (ED). The authors sought to validate the accuracy of FAST performed by surgeons during ED resuscitation of pediatric trauma patients. METHODS: Patients were assigned to one of three groups based on standard clinical criteria: immediate surgery, abdominal computed tomography (CT), or observation alone. FAST was then performed in the ED by a surgery resident (postgraduate year 3 or higher) or an attending trauma surgeon. Four views were used to assess the possible presence of fluid in the pericardial, subphrenic, subhepatic, and pelvic spaces. Time needed to conduct FAST was noted. Presence of peritoneal or pericardial fluid by FAST was compared with that determined by CT or surgery. Sensitivity, specificity, and predictive values were calculated. For those who did not undergo CT or surgery, FAST findings were compared with the clinical course. RESULTS: Technically adequate studies could be performed on 192 of 196 eligible children. Their ages ranged from 3 months to 14 years (mean, 6.9 years); 119 were boys (62%), and 188 (98%) had sustained a blunt injury. FAST was performed in a mean time of 3.9 minutes (range, 1-17 minutes). All FAST examinations were reviewed by our senior surgeon-sonographer (GSR). Interrater agreement between the performing and reviewing surgeon-sonographer was 100%. Sixty (31%) patients underwent either abdominal CT (n = 56; mean Injury Severity Score (ISS), 9.6) or immediate operation (n = 4; mean ISS, 18.8). Of the 10 patients with verified presence of intraperitoneal fluid, eight had positive and two had false-negative FAST examination results. Of the 50 patients with verified absence of intraperitoneal fluid, none had a positive FAST (ie, no false-positives); sensitivity was 80%; specificity, 100%; predictive value positive, 100%; predictive value negative, 96%. None of the 132 patients followed up clinically without CT or surgery (mean ISS, 4.5) had fluid documented by FAST, and all did well. CONCLUSIONS: The focused assessment for the sonographic evaluation of pediatric blunt trauma patients performed by surgical residents and attendings in the ED rapidly and accurately predicted the presence or absence of intraperitoneal fluid. The FAST is a potentially valuable tool to rapidly prioritize the need for laparotomy in the child with multiple injuries and extraabdominal sources of bleeding.
Abdominal Injuries↗
Induction of magnetic resonance-visible lipid in a transformed human breast cell line by tetraphenylphosphonium chloride.
Proton magnetic resonance spectroscopy (1H MRS) and DNA flow cytometry were used to monitor the effects of the cationic lipophilic phosphonium salt and potential antineoplastic agent tetraphenylphosphonium chloride (TPP) on the transformed human breast cell line HBL-100. TPP treatment for 48 hr was cytostatic at low concentrations and cytotoxic at higher concentrations with an IC50 of 55 microM as measured by Trypan blue exclusion. At micromolar concentrations, TPP caused a significant increase in the methylene MR signal arising from mobile lipid as measured by the ratio of the lipid CH2 peak height to either the CH3 peak height (internal referencing) or the peak height for p-aminobenzoic acid (PABA) as an external reference in a co-axial capillary within the sample. Over the same concentration range, TPP caused a slowing of passage through S phase as demonstrated by a significant depletion of cells in G2/M phase with a concurrent but non-significant increase in cells in S. Time-dependent increases in MR-visible lipid were observed with 2 microM TPP treatment, and the removal of TPP from the culture medium caused no significant reduction in mobile lipid. Two-dimensional 1H-1H COSY spectra of TPP-treated HBL-100 cells revealed concentration-dependent increases in cross-peak volume ratios arising from lipid acyl chains relative to both internal (lysine, polyamines) and external (PABA) standards. Increases in choline and glycerophosphocholine cross-peak volume ratios were observed, indicating that the catabolism or rearrangement of phospholipids may be responsible for the observed MR-visible lipid increases.
Adult↗
Auditory brainstem responses after ovariectomy and estrogen replacement in rat.
Previous work has suggested possible influences of ovarian hormones on evoked potentials in the auditory system. The aim of this project was to study the effects of ovariectomy and subsequent administration of estrogen replacement on the auditory brainstem response and the middle latency response. Groups of 90 day-old Long-Evans hooded rats were anesthetized for bilateral ovariectomies (ovex) and recordings made 3 weeks later. During the week prior to recordings some ovariectomized groups received subcutaneous injections of 10, 100 or 500 micrograms/kg Premarin in peanut oil, and other unoperated animals received vehicle injections. Recordings from vertex/chin using needle electrodes and pure tone stimulus parameters were made under Rompun/Ketamine. The results using 40 kHz tone stimuli showed that mean latencies for ovex animals were longer than animals in the 100 micrograms/kg Premarin group for waves 1a, 1an, 1b, 11, 111, 111n, and 1V/V. Other posthoc comparisons at 40 kHz stimulation revealed differences between control and 100 micrograms/kg Premarin groups for latencies of waves 1b, 1bn, 11 and 111. Latency reduction appeared for waves 1b, 1bn, 11 and 111 for the 10 ovex group, but only at wave 11 for the 500 ovex group, compared to ovex-only animals. Data from 8 kHz stimulation also demonstrated significant differences between the ovex and ovex 100 groups at waves 1bn and Vn. Observations of interpeak latency differences, especially between waves 1a and 11, suggested central as well as cochlear involvement in hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustic Stimulation↗
Measurements of acoustic impedance at the input to the occluded ear canal.
Multi-frequency (multi-component) acoustic impedance measurements may evolve into a sensitive technique for the remote detection of aural pathologies. Such data are also relevant to models used in hearing aid design and could be an asset to the hearing aid prescription and fitting process. This report describes the development and use of a broad-band procedure which acquires impedance data in 20 Hz intervals and describes a comparison of data collected at two sites by different investigators. Mean data were in excellent agreement, and an explanation for a single case of extreme normal variability is presented.
Acoustic Impedance Tests↗
Rate and frequency interactions in the auditory brainstem response of the adult rat.
Tone pip stimuli were used at different repetition rates to examine influences upon auditory brainstem response components. Rate increases to 80.1/s result in significant latency increases in waves IV and V at all test frequencies. Rate effects occur in rostral brainstem response components which show frequency related latencies different from wave I. Amplitude measures decline at higher repetition rates for waves I and IV at most test frequencies. Rate effects are most pronounced at 8 kHz stimulation which is around the optimal behavioral frequency in rat. At higher rates the second peak of wave I is enhanced at 8 kHz, whereas the third peak of wave I at 40 kHz disappears. These results demonstrate that tone-specific stimuli provide sensitive measures of latency, amplitude and wave morphology of components of the auditory brainstem response as a function of stimulus repetition.
Acoustic Stimulation↗
Comparison of SSPL90 selection procedures.
Recommended SSPL90 values were determined at 500, 1000, and 2000 Hz for 16 subjects with mild-to-moderate sensorineural hearing losses using six different selection procedures, including an Upper Limit of Comfortable Listening (ULCL) and threshold-based procedure by Cox (1988), a threshold-based procedure by Seewald and Ross (1988), and loudness discomfort procedures by Berger (1988), McCandless and Lyregaard (1983), and Hawkins et al (1987) and Libby (1985). Statistically significant differences were found among the procedures at 500 and 2000 Hz. Analysis of individual data showed that while some subjects obtained similar recommended SSPL90s across the procedures, others showed dramatically different values.
Adult↗
Effect of reference microphone location and loudspeaker azimuth on probe tube microphone measurements.
The effects of loudspeaker azimuth and reference microphone location on probe tube microphone measures were assessed. The real ear unaided response (REUR), real ear aided response (REAR), and real ear insertion response (REIR) were obtained on a KEMAR. Aided measures were obtained with both a behind-the-ear and an in-the-ear hearing aid. All three measurements were affected by changes in the loudspeaker azimuth and reference microphone location. Responses obtained with a 90 degree loudspeaker azimuth or with the reference microphone located at-the-ear revealed greater disparity than those obtained under other conditions. Most of the differences occurred at frequencies above 2000 Hz, with measurements utilizing the behind-the-ear hearing aid showing greater dispersion. These results suggest that the location of the loudspeaker and the reference microphone are important variables when utilizing probe tube microphone measurements.
Acoustics↗
Auditory brainstem responses to tonal stimuli in young and aging rats.
The auditory brain stem response (ABR) was studied in young adult and aged rats using 3,8 and 40 kHz tone pips. The expected inverse relationship between frequency and latency was observed in the younger group for waves I, II and III, while the response to the highest frequency stimulus had the longest latency at wave V. Absolute latencies for waves I through V each showed age-related increments with more pronounced changes occurring to 3 and 40 kHz stimuli than to the frequency of maximum sensitivity (8 kHz). Threshold increases with age for the highest frequency approximately doubled those for the lower frequencies. Examination of interpeak intervals (IPI) I-III, III-V and I-V revealed aging effects. The largest IPI I-V increment occurred to 3 kHz stimulation which reflects changes at both I-III and III-V sub-intervals. These results demonstrate electrophysiological correlates of aging due to transformations in the peripheral auditory system coupled with alterations in brainstem auditory pathways.
Acoustic Stimulation↗