Biomedical subjects
Publications and source records attributed to M K Ferguson.
The Nissen fundoplication currently is the most commonly used antireflux operation. It may be performed using a transabdominal or a transthoracic approach. Early postoperative complications are not infrequent and include dysphagia and the "gas bloat" syndrome. Excellent or good long-term results are obtained in more than 85% of patients.
Mesenteric lymph vessels exhibit spontaneous contractions that are critical in lymph fluid propulsion. We hypothesized that endothelium-derived relaxing factor (EDRF), recently identified as being released by lymph vessels, regulates contractile activity in mesenteric lymph vessels. Porcine mesenteric lymph vessel rings in vitro were administered either prostaglandin F2 alpha (PGF2 alpha; 10(-6) M), which increases contractile activity, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M), which blocks EDRF production, or PGF2 alpha + L-NMMA, while paired control vessel rings remained in Krebs buffer alone. Vessel segments stimulated with PGF2 alpha exhibited repetitive contractions with more regular rhythm and uniform morphology than control segments and significantly greater frequency, amplitude, and trough and active tensions. Inhibition of EDRF production significantly enhanced the frequency (3.9 +/- 0.5 vs 2.1 +/- 0.4 min-1) and amplitude (555 +/- 42 vs 378 +/- 62 mg) of basal spontaneous contractions compared to controls and appeared to elicit more uniform contractions with respect to rhythm and morphology. PGF2 alpha-stimulated vessels pretreated with L-NMMA demonstrated uniform contractions with significant increases in contraction frequency (6.3 +/- 0.7 vs 2.4 vs 0.9 min-1), amplitude (846 +/- 120 vs 495 +/- 99 mg), trough tension (738 +/- 146 vs -6 +/- 32 mg), and active tension (1584 +/- 192 vs 489 +/- 111 mg) compared to controls (P < 0.05 for each). The effects of L-NMMA on unstimulated vessels were reversed by the addition of L-arginine but not by D-arginine (10(-4) M for each).(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphatic smooth muscle tone and contractility are important determinants of lymph flow. Because we have shown previously that lymph vessels exhibit endothelium-dependent relaxation similar to that identified in blood vessels, we assessed the possible role of nitric oxide as an endothelium-dependent relaxant factor in lymph vessels using porcine tracheobronchial lymph vessel rings mounted in organ baths. Isometric active tension was measured and normalized as a percentage of response to 65 mM KCl-substituted perfusate. Histamine and NE elicited contraction in all vessel rings at a concentration of 10(-5) M, and we were unable to demonstrate relaxant responses to these substances even at low concentrations. In histamine- and NE-contracted vessel rings an increase in active tension was produced by NMMA (33.9 +/- 5.4 and 26.1 +/- 5%, respectively, P < 0.0001 for each), an effect that was reversed by addition of L-arginine but not by D-arginine. Endothelial disruption reversed the effects of NMMA in histamine-contracted (16.2 +/- 4.0% increase in active tension; P = N.S. vs initial histamine response) and in NE-contracted vessel rings (11.5 +/- 1.2% increase in active tension; P = N.S. vs initial NE response). The data provide evidence that nitric oxide is an endothelium-dependent relaxant factor that regulates tracheobronchial lymphatic smooth muscle tone and is released in response to administration of contractile agonists.
The use of transcervical thymectomy in the treatment of myasthenia gravis remains controversial. We retrospectively reviewed our experience with this procedure to determine its usefulness in the management of myasthenia gravis. Fifty-three selected myasthenic patients without thymoma underwent transcervical thymectomy between 1977 and 1991. The mean age (27.5 +/- 1.5 years), duration of symptoms (2 +/- 1.0 years), and preoperative Osserman classification (13% class I, 53% class IIA, 28% class IIB, 6% class III) were consistent with previous reports. The average hospitalization was 3.0 +/- 0.3 days, but has been 1.6 +/- 0.2 days since 1987 (n = 14). There were no deaths, and no patients required mechanical ventilation for more than 24 hours. Average follow-up was 4.3 +/- 0.4 years with a range of 0 to 13 years. Eighty-one percent of patients are symptom free, and 9 of 21 (43%) are in complete remission at least 5 years postoperatively. One patient required a transsternal exploration for worsening symptoms. Clinical improvement continued over an extended period of time, and a statistically significant decrease in symptoms was evident comparing the first and sixth postoperative years. Patients were more likely to be improved or in remission if thymectomy was performed within the first year of the onset of symptoms (p < 0.05). Osserman classification, thymus histology, and patient age were not prognostic indicators. Transcervical thymectomy is effective surgical therapy for myasthenia gravis in selected patients without thymoma.
Concomitant chemoradiotherapy represents an investigational approach to the treatment of locoregionally advanced non-small cell lung cancer. The theoretical rationale, and clinical experience are reviewed in brief. Clinical trials conducted at the University of Chicago are summarized.
Peptic esophageal strictures usually respond to intensive medical therapy and dilation. Failure of such management necessitates surgical intervention, usually consisting of dilation and fundoplication, for which results are good. More complex problems require gastroplasty, acid suppression and alkaline diversion, or resection; outcomes of these operations are not as favorable.
We performed morphometric and length-tension analyses comparing mesenteric and tracheobronchial lymph vessel segments to determine the potential of the latter tissue to regulate pulmonary and mediastinal lymph flow via alterations in smooth muscle tone. Fresh porcine lymph vessel rings were prepared for 1) in vitro assessment of length-tension relationships and 2) histologic preparation and measurement of smooth muscle cross-sectional area (SMA). Mesenteric and tracheobronchial optimal vessel ring lengths were 3.1 +/- 0.2 and 3.5 +/- 0.2 mm, and maximum active tensions were 1518 +/- 25 and 1703 +/- 162 mg. Smooth muscle formed indistinct layers in each tissue, and only 30% of the smooth muscle was oriented circumferentially. Stress generated by the circular smooth muscle was similar to that generated by other types of vascular smooth muscle. In 75% of mesenteric vessel rings spontaneous contractions were observed that had a mean contraction frequency of 1.7 +/- 0.2 min-1 and a mean contraction amplitude of 349 +/- 35 mg, while only 40% of tracheobronchial vessels exhibited spontaneous contractions (p < 0.001) that had a mean frequency of 0.6 +/- 0.2 min-1 (p = 0.0021) and a mean contraction amplitude of 118 +/- 10 mg (p < 0.0001). We conclude that tracheobronchial lymphatic vascular smooth muscle is capable of developing stress similar to that generated by mesenteric lymph vessels, and that spontaneous rhythmic contractile activity is qualitatively and quantitatively different in tracheobronchial than in mesenteric porcine lymph vessels. The data suggest that tracheobronchial lymph vessels are capable of regulating pulmonary and mediastinal lymph flow through intrinsic mechanisms. Such regulation may occur by alterations in vascular resistance rather than via spontaneous pumping activity.
BACKGROUND: Dedifferentiated chordoma is an unusual and aggressive variant of chordoma which is likely to metastasize. Few reports exist of treatment of these tumors with chemotherapy. METHODS: In 1988, two patients with dedifferentiated sacral chordomas were seen at the University of Chicago Hospitals. Both developed metastatic disease less than a year after sacral resection and radiation therapy. These patients' diagnoses, courses, and treatments were reviewed along with the literature on chemotherapy in both conventional and dedifferentiated chordomas. RESULTS: Both patients obtained complete remissions, one to a six-drug regimen and the other to ifosfamide. CONCLUSIONS: A trial of reasonably aggressive chemotherapy is warranted in patients with metastatic dedifferentiated chordoma. The optimum regimen is unclear, but agents active in high-grade sarcomas are logical choices.
As the population continues to age, older patients are being referred for thoracic surgical procedures with increasing frequency. From 1985 through 1992, 38 patients (32 men, 6 women) 70 years of age or older underwent esophagectomy for primary esophageal carcinoma. Histologic findings included adenocarcinoma in 28 (74%) and squamous carcinoma in 10 (26%). Patients suffered dysphagia for a mean of 3.8 months (range, 0 to 30 months) and had a mean weight loss of 5.8 kg (range, 0 to 22 kg). The tumors ranged from 1 to 14 cm in length and averaged 4.7 cm. Preoperative chemotherapy and radiation therapy were administered in 11 patients (46%). Clinical staging suggested all patients were curable, and esophagectomy was performed in a transthoracic fashion in 27 (71%) and from a transhiatal approach in 11 (29%). Cervical anastomoses were undertaken in 16 patients (42%). The mean blood loss was 1,165 mL and ranged from 500 to 4,000 mL. The mean number of transfused units was 2.3 (range 0 to 8 U). Overall operative mortality was 18% (7 of 38). Major morbidity included pneumonia in 11 (29%), anastomotic leak in 4 (11%), chylothorax in 4 (11%), pulmonary embolus in 3 (8%), and stroke and myocardial infarction in 1 patient each (3%). Three patients have been cured of their esophageal cancer with survivals of 65, 70, and 72 months and an additional 7 patients are still alive. Three patients (8%) have been lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
The management of complications affecting the pleural space is sometimes technically demanding, but has been enhanced by the recent introduction of thoracoscopic techniques. An empyema in the fibrinopurulent phase is best managed by disruption of the loculations and complete drainage of the infected space. This is easily accomplished with the use of thoracoscopy, which also permits inspection of the pleural space to determine whether additional surgical intervention is required. In contrast, thoracoscopy is not indicated in the management of a free-flowing empyema or a chronic empyema associated with a fibrous capsule. Bronchopleural fistulas are occasionally treated by thoracostomy tube drainage alone, but, in most situations, surgical intervention is necessary to permit reclosure of the bronchus, coverage of the stump with vascularized tissue, and decortication or tissue flap rotation to fill the pleural space. These maneuvers are beyond the capabilities of current thoracoscopic techniques. Chylothorax is best treated initially by intercostal tube drainage and supportive measures. When surgical intervention is necessary to directly close a lymph vessel leak, thoracoscopic techniques have been successful in effecting closure, according to anecdotal reports.
Diffuse lung diseases due to a wide variety of conditions are amenable to diagnosis by means of clinical evaluation, bronchoalveolar lavage, transbronchial biopsy, and lung biopsy. The recently introduced technique of thoracoscopic wedge biopsy provides the potential advantages of greater selection of biopsy sites and reduced postoperative pain compared with that associated with standard open lung biopsy. Its overall accuracy cited in initial reports has exceeded 90%. Although it is supplanting open lung biopsy as the most common operative technique for diagnosing diffuse pulmonary abnormalities, the availability of thoracoscopic lung biopsy should not alter the current indications for the initial use of bronchoscopic techniques in selected patients. In addition, because of the additional risk carried by thoracoscopic lung biopsy, open lung biopsy should still be used preferentially in patients suffering from acute decompensation, pulmonary hypertension, or coagulation disorders.
Closure of massive soft-tissue defects in patients undergoing forequarter amputation for shoulder-girdle tumors may present a daunting challenge. This report describes two patients whose forequarter amputations were closed using ipsilateral, lymphedematous, circumferential forearm fasciocutaneous free flaps.
Synchronous primary lung cancers (SPLCs) occur in up to 0.5% of patients with lung cancer. They are first diagnosed intraoperatively or upon pathologic examination of resected tissue in up to 40% of patients with SPLCs. Complete surgical resection is possible in over 90% of patients, with an operative mortality of 2.1%. Despite a high frequency of early stage disease (two thirds of patients have either stage I or II tumors), surgical therapy yields an overall 5-year survival of only 20%, far lower than expected. These findings suggest that the biology of SPLCs is different from that of ordinary lung cancers, or that the diagnosis of SPLCs is being made too often, and that in some patients the second cancer focus actually represents metastatic disease. The use of newer techniques of identifying the molecular and biologic characteristics of these cancers, including analysis of DNA ploidy patterns, may more accurately define SPLC patients. Optimal interventional and preventive therapies remain to be determined.
We assessed the responsiveness of tracheobronchial lymphatic smooth muscle to mediators of inflammation to determine whether homogeneous responses to histamine and 5-hydroxytryptamine (5-HT) are demonstrated among species typically used in studies of lymph vessels. Fresh porcine and bovine tracheobronchial lymph vessels were suspended from force-displacement transducers in baths containing oxygenated Krebs solution. Concentration-response curves were generated by cumulative addition of histamine (10(-7) to 10(-3) M) or 5-HT (10(-7) to 3 x 10(-4) M). Active tension (AT) was expressed in milligrams and as a percentage of initial vessel ring response to 65mM KCl. Histamine elicited concentration-dependent contraction, yielding maximum AT in porcine rings of 1116 +/- 127 mg (n = 39; 129.1 +/- 10.5% of KCl response) and in bovine rings of 733 +/- 106 mg (n = 20; 65.8 +/- 12.9%; P = 0.0005 for percent responses). PD2 values (negative log10 of the concentration at half-maximum effect) were 4.49 +/- 0.08 and 4.82 +/- 0.08; (P = 0.0034). 5-HT elicited concentration-dependent contraction, yielding maximum AT of 560 +/- 50 mg in porcine rings (n = 15; 97.2 +/- 9.7%) and 2892 +/- 454 mg in bovine rings (n = 27; 159.0 +/- 29%; P < 0.0001 for percent responses). PD2 values were 6.25 +/- 0.05 and 5.28 +/- 0.04 (P < 0.0001). The data demonstrate a role for inflammatory mediators in the modulation of tracheobronchial lymphatic smooth muscle tone that is species- and mediator-specific, and support the potential for paracrine regulation of tracheobronchial lymph flow.
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Current information regarding the physiology of lymphatic smooth muscle is derived from experiments on mesenteric and thoracic duct lymph trunks. We hypothesized that tracheobronchial lymphatics share many of the same properties possessed by the mesenteric lymphatics, and examined the passive and active length-tension characteristics of the two. Fresh isolated lymph vessel rings were prepared from bovine mesenteric and tracheobronchial lymphatic collectors, mounted in organ baths, and connected to force-displacement transducers. Isometric contractions were induced by exposure to 65mM KCl-substituted perfusate after intermittent ring length changes. Active tension was calculated. Optimal vessel length was greater in tracheobronchial vessel rings, averaging 4.9 +/- 0.4mm vs 2.8 +/- 0.3mm in mesenteric rings (p < 0.001). Optimal resting tension and ATmax were similar for both truncal types, measuring 738 +/- 95mg and 2379 +/- 289mg in tracheobronchial vessel rings, and 625 +/- 108mg and 2501 +/- 320mg in mesenteric vessel rings, respectively. Stress developed at L(o) (optimal length) was similar for tracheobronchial (35.4 +/- 4.3mN mm-2) and mesenteric (26 +/- 4.3mN mm-2) lymphatics (P = N.S.). The data demonstrate that tracheobronchial lymph vessels are similar to mesenteric lymph vessels in their ability to generate significant stress, and suggest that these lymphatics participate in the regulation of lymph flow.
The endothelium regulates smooth muscle tone in blood vessels through the release of endothelium-deprived relaxing factor (EDRF). We hypothesized that the lymphatics possess endothelium-dependent relaxant properties analogous to those in blood vessels. Fresh porcine tracheobronchial lymphatic vessel rings were mounted in organ baths and connected to force-displacement transducers. Rings were submaximally precontracted with 10(-5) M histamine and exposed to cumulative addition of acetylcholine (ACH; 10(-7)-3 x 10(-4) M) or bradykinin (BRD; 10(-8)-3 x 10(-6) M), both of which are known to promote release of EDRF. ACH caused concentration-dependent relaxation (maximum effect = -2.3 +/- 2.6% of initial histamine-induced active tension), while a similar but less pronounced effect was seen with BRD (39.6 +/- 5.4%). The relaxant effects of ACH and BRD were inhibited by collagenase pretreatment and mechanical endothelial denudation. The results confirm our hypothesis that lymphatic vessels possess endothelium-dependent relaxant properties and suggest that lymph vessels can regulate lymph flow through processes similar to those found in blood vessels.
Forty-nine consecutive patients with pathologic Stage II non-small-cell lung cancer treated over a 15-year period were retrospectively reviewed. The treatment strategy evolved during the period of review. Early patients were treated with surgery alone (S); subsequent patients were treated with adjuvant radiation therapy (SR); and more recent patients were treated with postoperative chemotherapy and radiation therapy (SRC). Fifteen patients received S alone, 10 patients received SR, and 24 patients received SRC. The median survival time (MST) of all 49 patients was 20 months, and the estimated 5-year survival was 25%. The MST of patients in each of the three treatment arms was S-6 months; SR-19 months; and SRC-25 months. The majority of patients died from systemic relapses or second primary lung cancers. The addition of adjuvant therapy (SR, SRC) significantly improved the MST of patients compared to surgery alone (S). The overall survival of patients did not change between treatment arms.