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Biomedical subjects

L D Hill

Publications and source records attributed to L D Hill.

At least 19 recordsLinked to original sources

Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line.

The third component of C, C3, is the key opsonin of the C cascade and is produced locally within the lung by pulmonary epithelial cells, macrophages, and fibroblasts. Because glucocorticoids regulate the maturation and expression of several physiologically important genes in pulmonary epithelial cells, we examined the effects of glucocorticoids on C3 mRNA expression and C3 synthesis by the human pulmonary epithelial cell line, A549. Treatment with dexamethasone enhanced C3 production in a time- and dose-dependent fashion such that concentrations of dexamethasone greater than or equal to 0.001 microM significantly increased C3 production on day 3 of culture. Natural glucocorticoids, corticosterone, cortisol, and 11-deoxycortisol also increased C3 concentrations in A549 supernatants. Both cycloheximide and the glucocorticoid receptor antagonist, RU486, individually inhibited the effect of dexamethasone on C3 production. Northern analysis demonstrated that the steady state 5.2-kb C3 message increased in A549 cells within 10 h of treatment with dexamethasone. RU486 inhibited the effect of dexamethasone on C3 mRNA expression. The integrity of the C3 thiolester bond, as measured by [3H]iodoacetic acid titration and hemolytic assay, was not disrupted by dexamethasone. We conclude that glucocorticoids such as dexamethasone enhance the expression of C3 mRNA and increase the production of functionally active C3 by A549 cells by a mechanism that is mediated by the intracellular glucocorticoid receptor.

Cell Line

Use of purified streptokinase in empyema and hemothorax.

Enzymatic debridement of the pleural cavity for retained hemothorax or empyema is a frequently overlooked option. Thirteen of fourteen patients (93%) with retained pleural collections underwent successful enzymatic debridement and tube drainage with purified streptokinase injections. The average increase in chest tube output following streptokinase injections was 158%. No significant adverse reactions occurred. One patient required thoracotomy when streptokinase therapy failed. Two others had successful resolution of their pleural collections but required thoracotomy for other indications. There were two deaths (14%), which were unrelated to the use of streptokinase or residual empyema. Intrapleural streptokinase is a safe, effective means of removing retained proteinaceous collections in the pleural space. It is a useful adjunct to chest tube drainage and may obviate the need for more invasive procedures.

Adult

Antireflux surgery. A surgeon's look.

With a reassessment of the antireflux barrier, we are gaining a better appreciation of the components of the barrier and their importance in preventing reflux. The GE valve in particular appears to play a key role in preventing reflux. With better understanding of the anatomy and function of the GE barrier, we should do a better job, both medically and surgically. The knowledge and new technology that are available should allow the surgeon to perform antireflux surgery with 95% good to excellent results with a minimum of morbidity. As our 15 to 20 year follow-up with a mean of 17.8 years shows, these good results will last over the long term. These observations should give the gastroenterologist confidence that antireflux surgery is highly effective for those patients who fail medical management.

Barrett Esophagus

Colorectal neodymium-YAG photoablative therapy. Comparing applications and complications on both sides of the peritoneal reflection.

Laser photoablative therapy has seen wide application in the esophagus, stomach, and rectum. Its use in the supraperitoneal colon has been less extensive because of fear of complications. One hundred fifteen patients who presented during a four-year period and underwent neodymium-YAG laser treatment on both sides of the peritoneal reflection (rectum, 47 patients; colon, 68 patients) were reviewed. The various lesions treated with laser therapy included 32 malignant tumors that presented with bleeding or obstruction, 44 large broad-based villous adenomas, six carcinoid tumors, and 33 patients with arteriovenous malformations or radiation proctitis who presented with acute hemorrhage or chronic blood loss. Overall treatment efficiency was 83% in the rectal group vs 87% in the colonic group. There was no significant difference in complication frequency or severity between the two groups, even though 45% of the colonic lesions were located in the thin-walled cecum. There was no laser-related mortality in this series. Laser photoablative therapy is safe and effective treatment for a wide variety of colorectal lesions. In experienced hands, it can be used on either side of the peritoneal reflection with equal efficiency and no increased risk of complications.

Adenoma

Fifteen- to twenty-year results after the Hill antireflux operation.

Antireflux surgery, specifically the Hill procedure, has been shown to be effective management of refractory reflux when assessed in the relatively short term. This study follows 441 patients from the time of their initial operation and reports on assessments conducted after 5 to 10 years and 15 to 20 years. The late study group comprises 167 patients (mean age 71 years) with an average follow-up of 17.8 years; 15.6% of patients had undergone a previous antireflux operation. Overall subjective good and excellent results, as determined by the patients themselves, were seen to improve significantly (p less than 0.02) between the two follow-up periods, 82% and 88%, respectively. No serious late complications such as fistula, bleeding, or obstruction were observed in this series. The Hill antireflux operation, properly performed, provides durable long-term results.

Adolescent

Cervical esophageal web associated with Zenker's diverticulum.

We reviewed 12 patients who underwent diverticulectomy and myotomy for Zenker's diverticulum. Fifty percent of these patients were found to have cervical esophageal webs that were resected at operation. The association of Zenker's diverticulum and esophageal webs is new. The present study demonstrates that it is not a rare relationship and that these webs can cause postoperative problems. We utilized the technique of open diverticulectomy and found that it facilitates cricopharyngeal myotomy and allowed intraoperative inspection of the esophageal lumen, thereby patients with coexisting intraesophageal pathologic abnormalities could be identified. This procedure can be performed within very acceptable limits of morbidity, as demonstrated in our study, although it is not recommended for surgeons who do not regularly operate on the esophagus. Surgeons should consider this technical approach to Zenker's diverticulum when the presence of cervical webs is known or suspected preoperatively. Cervical esophageal webs are a potential source of postoperative dysphagia. They should therefore be excised when encountered intraoperatively. The actual incidence of cervical esophageal webs and their potential role in the pathogenesis of cricopharyngeal muscle hypertrophy and Zenker's diverticulum will require additional study.

Aged

Post Nissen syndrome.

The Nissen fundoplication is the most common anti-reflux operation performed. Gas bloat and inability to vomit after repair may be severe, but infrequently require reoperation; in contrast, other complications can be very debilitating or life-threatening. One hundred and sixteen patients who required reoperation for serious complications after Nissen repair are presented and classified according to the cause of the failed repair. Nissen complications resulted in recurrent reflux (86 per cent), severe dysphagia (60 per cent), esophageal dysmotility (48 per cent) and gastric perforation and fistualization (5 per cent). The "classic" Nissen fundoplication involves a blind 360 degree wrap, which includes the acid-producing parietal cell mass. The resulting pouch drains poorly and is, therefore, subject to gastric ulceration. Reoperation at our institution, using principally the Hill antireflux procedure, gave excellent or good results in 86 per cent, fair in 9 per cent and poor in 5 per cent. Three operative deaths (2.6 per cent) and one late death (0.9 per cent) occurred.

Adolescent

Improved results of surgical treatment for esophageal and gastroesophageal junction carcinomas after preoperative combined chemotherapy and radiation.

Combined treatment with chemotherapy and radiation (chemoradiation) preceding surgical exploration for esophageal or gastroesophageal squamous cell carcinoma or adenocarcinoma was compared with surgical exploration alone to determine if there was an influence on tumor status at exploration, tumor resectability, disease recurrence, and patient survival. Preoperative chemoradiation resulted in significant tumor response as measured by decreased nodal involvement and 36% incidence of no residual tumor at resection (total response) and was reflected by an improvement in resectability. Local tumor recurrence was eliminated by preoperative chemoradiation preceding resection. Distant recurrence was not reduced and remained the major cause of death. The 2-year survival rate after tumor resection alone was 33% versus 66% after preoperative chemoradiation and resection (p = 0.13). Patient survival after resection alone was predicted by pathologic extent of local disease as measured by lymph node status. In contrast, survival after chemoradiation and resection was not predicted by pathologic extent of local disease. Surgical resection appears to have been an important component of therapy, primarily because survival was improved in patients after resection of residual local disease.

Actuarial Analysis

Reappraisal of the flap valve mechanism in the gastroesophageal junction. A study of a new valvuloplasty procedure in cadavers.

This study in cadavers was carried out to resolve whether a functional flap valve exists at the gastroesophageal (GE) junction and whether an accentuation of this valve (valvuloplasty) could increase the GE pressure gradient. Cadavers were investigated with open manometry catheters in the esophagus and stomach. Stepwise (50 ml) filling of the stomach demonstrated a GE pressure gradient of 4.6 +/- 1.6 cmH2O. This gradient could be significantly increased to 12.5 +/- 3.1 cmH2O (p less than 0.05) by performing a valvuloplasty procedure through a gastrostomy. By depressing the fundus of the stomach, the angle of His was made more obtuse and the flap valve component eliminated. This maneuver resulted in reflux in all cadavers before as well as after valvuloplasty. These experiments and observations taken together with our valvuloplasty procedure, confirm that a flap valve mechanism exists at the GE junction.

Adult

Reoperation after failed esophagomyotomy for achalasia.

Of 49 patients with achalasia treated surgically between 1975 and 1985, 12 (8 women, 4 men) had undergone transthoracic esophagomyotomy previously. Four had had concomitant upper gastrointestinal surgery. All 12 patients complained of dysphagia; other symptoms included regurgitation, nocturnal aspiration, heartburn, chest pain, vomiting, upper gastrointestinal bleeding and weight loss. The average time from initial operation to onset of symptoms was 9 months. Preoperative investigations and operative findings identified the cause of dysphagia as inadequate or healed esophagomyotomy with persistent or recurrent achalasia (eight patients--two had partially disrupted fundoplications contributing to their dysphagia), hiatus hernia with reflux esophagitis causing esophageal spasm or peptic esophageal stricture (two patients) and incorrect initial diagnosis and treatment (two patients). Treatment, with the aid of intraoperative manometry, included repeat Heller myotomy (five patients), Hill antireflux repair (four patients), takedown of Nissen fundoplication and extension of myotomy (two patients). The average follow-up was 16 months. Eight patients had good results, two required further operation and one underwent multiple dilatations postoperatively. The causes of recurrent dysphagia following surgery for achalasia are diverse and patients require individualized investigation and treatment. Remedial surgery for achalasia can correct postoperative dysphagia but results are less successful than those following an adequate initial operation.

Adolescent

Surgical management of peptic esophageal stricture. Twenty-year experience.

The consensus in the conflict about surgical management of peptic esophageal stricture presently favors conservative antireflux procedures with dilatation rather than resection. However, emphasis is now shifting to the controversy of conservative surgical treatment versus medical management with dilatation alone. We analyzed the influence of seven variables on the postoperative result in 160 patients undergoing antireflux operations with dilatation for peptic esophageal stricture. The mean follow-up is 47 months (range 6 to 240) and the mean age is 57 years (range 13 to 83). One hundred seven patients operated on early in the course of the disease have better results (90% good, 9% fair, 1% poor) than 31 patients having a previous failed operation (52% good, 23% fair, 26% poor) and 22 patients having multiple dilatations (45% good, 23% fair, 32% poor) (p less than 0.05). Intraoperative manometry improves results (p less than 0.05), and postoperative reflux has a negative influence on results (p less than 0.05). The postoperative lower esophageal sphincter pressure in patients without reflux (17.7 +/- 1.3 mm Hg) is higher than in those with reflux (8.9 +/- 0.8 mm Hg, p less than 0.05) and is an accurate predictor of the risk of reflux (p less than 0.001). Intraoperative and postoperative sphincter pressures are objective indicators of outcome but because of variability are not predictive (p less than 0.05). The presence of Barrett's esophagus and the age and sex of patients do not alter outcome. Adenocarcinoma did not develop in patients with Barrett's esophagus once reflux was eliminated. This information indicates that conservative antireflux operation with dilatation is the treatment of choice in patients with peptic esophageal stricture.

Adolescent

Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials.

The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants.

Adult

Intradiaphragmatic abscess. An extremely rare complication of pneumatic dilatation of the esophagus.

A patient with dysphagia initially diagnosed as achalasia but now thought to have spinocerebellar degeneration manifesting itself in the esophagus as achalasia, developed an intradiaphragmatic abscess, presumably as a complication of pneumatic dilation of the esophagus. This previously unreported complication occurred as a result of transmural spread of bacteria at the time of dilatation with seeding of the diaphragmatic muscle. An intradiaphragmatic abscess may be mistakenly diagnosed clinically and radiologically as a subphrenic abscess or loculated empyema. Management of intradiaphragmatic abscess is discussed briefly.

Abscess

Effect of obesity on esophageal transit.

Esophageal transit time as measured by radionuclide scintigraphy using a swallowed technetium sulfur colloid bolus was measured in obese patients with gastroesophageal reflux, lean patients with reflux, and lean volunteers without reflux. The esophageal transit time was significantly prolonged in the obese group compared with both lean groups (p less than 0.001). Esophageal manometric measurement also confirmed that obese patients have an elevated gastroesophageal pressure gradient, presumably caused by increased intraabdominal pressure resulting from the mechanical burden of excess fat. The esophageal transit time is significantly related to the gastroesophageal pressure gradient. This finding, coupled with those in previous manometric investigations showing that esophageal muscle has a decreased maximum velocity with increasing afterload, explains in part why obese patients have delayed esophageal transit time. Therapy for reflux in obese patients should be aimed at improving esophageal transit.

Adult

Contributions of behavior modification to cerebral palsy habilitation.

The application of behavior modification techniques to cerebral palsy habilitation combines behaviorist psychology and physical therapy. In working together, physical therapists and behaviorists have a great deal to offer children and adults with cerebral palsy. I present a behaviorist perspective on how cerebral palsy affects an individual's interactions with the environment and how the environment can be modified to teach and improve motor functioning. The usefulness of this perspective in guiding physical therapy is discussed and research in which behavior modification has been used in cerebral palsy habilitation is reviewed.

Adolescent

A randomized comparison of the effects of adjuvant therapy on resected stages II and III non-small cell carcinoma of the lung. The Lung Cancel Study Group.

The Lung Cancer Study Group has evaluated postoperative chemotherapy and immunotherapy in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients were randomized following surgery and careful intraoperative staging to receive either chemotherapy or immunotherapy. Chemotherapy consisted of CisPlatinum, Adriamycin, and Cytoxan and immunotherapy consisted of Levamisole and Intrapleural BCG. Sixty-eight patients were randomized to the immunotherapy arm and 62 to the chemotherapy arm. There were 49 recurrences in the immunotherapy group and 35 in the chemotherapy group (p = 0.003). These studies indicate that surgical adjuvant chemotherapy is effective in prolonging the disease-free survival in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients with Stages II and III resected squamous cell carcinoma were randomized to receive postoperative radiation therapy or no further treatment. One hundred and ninety patients were randomized into this study. There was no significant difference in terms of survival between the two treatment groups. However, those who received radiation therapy had a significantly lower incidence of local recurrence (p = 0.001). These studies indicate that postoperative radiation therapy is effective in controlling the local disease but that effective systemic therapy is necessary for improved survival in patients with Stages II and III squamous cell carcinoma of the lung.

Adenocarcinoma

Use of I-131 labeled, murine Fab against a high molecular weight antigen of human melanoma: preliminary experience.

High molecular weight antigen (HMWA) is a tumor-associated proteoglycan of human malignant melanoma. I-131 labeled Fab fragments of these specific antibodies were used for preliminary feasibility studies for radioimmunodetection and therapy of human subjects who had inoperable metastatic melanoma. Ten patients received tracer doses of 5-13 mCi (185-481 MBq) of I-131 (anti-HMWA) Fab. All patients (8/8) who had melanoma lesions greater than 1 cm by correlative diagnostic methods had one or more lesions that had localization to tumor of the radiolabeled Fab. In all, 17 of 23 (74%) documented metastases were seen. There were no false positives in this series. Two patients who had avid uptake received potentially radiotherapeutic doses of 142 mCi (5,254 MBq) (one patient) and 181 mCi (6,697 MBq) and 193 (7,141 MBq) (total: 374 mCi or 13,838 MBq) (one patient). For both of these patients, whole body imaging studies showed that the localization of the high dose I-131 Fab was predominantly in tumor. The patient who received the larger dose showed a greater than 50% reduction in the size of pelvic and pericaval nodes, with stabilization of disease at the smaller nodal size for a period of three months. On whole body images, the anti-Fab HMWA appears to be more tumor selective than Fab preparations that target the p97 antigen for melanoma, and there is less uptake in liver.

Animals