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Biomedical subjects

E Watkins

Publications and source records attributed to E Watkins.

At least 19 recordsLinked to original sources

Ten to 20-year clinical results after short esophagomyotomy without an antireflux procedure (modified Heller operation) for esophageal achalasia.

To determine the long-term clinical results after modified esophagomyotomy without an antireflux procedure for esophageal achalasia, the status of all patients undergoing this operation with a minimum follow-up time of 10 years was reviewed; 81 such patients were operated on between January 1970 and January 1981. Thirteen patients were lost to follow-up review permitting clinical evaluation during the past year of 68 patients (84%) observed for a median of 13.6 years. Fifty-nine patients (87%) were improved by operation; 90% of the patients who underwent a primary procedure were improved, whereas only 73% of patients undergoing reoperation benefited. Kaplan-Meier analysis of the results of all 81 patients disclosed an improvement rate of 98.5% at 5 years, 95.6% at 10 years, 85.8% at 15 years, and 67.3% at 20 years. When the level of improvement or lack thereof was analyzed, the percentage of excellent results decreased from 54% to 32% (P = 0.02). The percentage of good results remained the same, whereas fair or poor results together increased from 20% to 37% (P = 0.05). Neither age, sex, esophageal caliber, duration of symptoms, or previous therapy appeared to influence these results. We conclude that limited esophagomyotomy without an antireflux procedure results in persistent long-term improvement for the patient with esophageal achalasia. The level of improvement, however, decreases with the passage of time, presumably because of persistent disease in the body of the esophagus leading to impaired esophageal emptying in some patients and late reflux esophagitis in other patients owing to poor esophageal clearance.

Adolescent

Barrett's esophagus. Prevalence and incidence of adenocarcinoma.

Between January 1973 and January 1989, 241 patients with Barrett's esophagus were treated at the Lahey Clinic Medical Center, Burlington, Mass. Of these patients, 65 presented with adenocarcinoma in Barrett's esophagus for a prevalence rate of 27%. Of 176 patients followed up for a total of 497 patient-years, adenocarcinoma developed in five patients for an incidence of one per 99 patient-years. The development of adenocarcinoma during endoscopic surveillance 1, 2, 2, 4, and 10 years after the initial diagnosis of Barrett's esophagus emphasizes the importance of long-term endoscopic and histologic surveillance. All five patients had severe dysplasia before adenocarcinoma developed. Yearly endoscopic follow-up examination is recommended for all patients with Barrett's esophagus unless mild dysplastic changes are found, in which case surveillance should be increased. Patients with severe dysplasia who are otherwise acceptable candidates for operation should be advised to have esophageal resection.

Adenocarcinoma

Pathologic review of consecutive radical prostatectomy specimens. Nerve sparing versus nonnerve sparing.

Retrospective pathologic analysis was conducted of specimens from 88 radical retropubic prostatectomy operations performed between 1982 and 1987 inclusive. The median age of patients was sixty years (range, 46 to 73 years). Of the 88 radical prostatectomies performed, 51 were nerve-sparing (40 bilateral) and 37 were nonnerve-sparing (11 unilateral) procedures. Preoperative clinical staging was similar in both groups. Thirty-five of 37 patients (95%) in nonnerve-staging group and 51 of 51 patients (100%) in nerve-sparing group had clinical Stage B2 disease or less. Pathologic staging in both groups was also similar. In 26 of 37 patients (70%) in nonnerve-sparing group and in 35 of 51 patients (69%) in nerve-sparing group, disease remained localized to the prostate. Both groups were analyzed retrospectively to determine whether or not the incidences of microinvasion of capsule and of extraprostatic disease differed. Review of the apical and lateral margins of the specimens revealed no statistically significant difference in either the degree of microinvasion of capsule or the incidence of extraprostatic disease between the groups.

Adenocarcinoma

Adenocarcinoma in Barrett's esophagus. A clinicopathologic study of 65 cases.

The natural history of Barrett's esophagus, particularly the prevalence and incidence of malignant changes in it, remains controversial. Furthermore the prognosis of surgically treated patients with carcinoma in Barrett's esophagus has not been elucidated fully. To examine these and other issues, the records of 65 patients with carcinoma in Barrett's esophagus presenting at the Lahey Clinic Medical Center from January 1973 to January 1989 were reviewed. During this period, 241 patients with documented Barrett's esophagus were seen, for a prevalence of carcinoma of 27%. Adenocarcinoma in Barrett's esophagus accounted for 30% of the surgically treated carcinomas of the thoracic esophagus during this period. All but four of these patients were men. Symptoms of chronic reflux were present in less than one half of the patients and dysphagia was often the presenting symptom. In eight patients the carcinoma was discovered on routine surveillance endoscopy, and in four patients progression of disease from benign columnar epithelium to dysplasia to carcinoma was documented. Tumors developed in six patients who had undergone previous antireflux surgery, and in four other patients a second carcinoma developed in residual Barrett's epithelium after a previous resection. Of the 65 patients, 61 (94%) were considered to have operable disease, all of whom underwent resection. Two patients (3.3%) died within 30 days of operation. The resected specimens were staged as follows: stage 0, 4; stage I, 10; stage II, 17; stage III, 25; stage IV, 4. Of the resected specimens, 73% showed areas of dysplasia adjacent to the tumor. The overall adjusted actuarial 5-year survival rate was 23.7%. The 3-year survival rate was 100% for patients with stage 0 carcinoma, 85.7% for patients with stage I carcinoma, 53.6% for patients with stage IIA carcinoma, 45% for patients with stage IIB carcinoma, 25.2% for patients with stage III carcinoma, and 0% for patients with stage IV carcinoma. The premalignant nature of Barrett's esophagus requires endoscopic surveillance to detect early carcinoma because symptoms often occur late or are absent. Antireflux surgery does not protect against the development of carcinoma. All of the Barrett's epithelium must be resected because a second carcinoma may develop in residual columnar epithelium. Severe dysplasia should be considered an indication for resection. Although operability and resectability rates are high, long-term survival is not. Early detection is mandatory if long-term survival is to be achieved.

Adenocarcinoma

Long-term results of pancreatic resection and segmental pancreatic autotransplantation for chronic pancreatitis.

Thirteen patients who underwent extensive pancreatic resection and segmental autotransplantation and who have a median follow-up of 62 months are presented. Eleven patients had technically successful grafts. Three of six patients who underwent total pancreatectomy and three of five patients who underwent near-total resection remain insulin-independent. Those patients who require insulin require small doses and have stable diabetes. Pain has recurred in 7 of the 11 patients who underwent distal subtotal resection; 5 of them required pancreatoduodenectomy and completion pancreatectomy for pain relief. Because of the high rate of recurrence of pain after distal resection, we favor pancreatoduodenectomy as the initial procedure of choice. When distal near-total or total pancreatectomy is required, the addition of segmental autotransplantation offers definitive, although at times transient, benefits in glucose homeostasis compared with no transplantation.

Adult

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine.

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.

Adult

Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Adolescent

Structure of an ectodermally expressed sea urchin metallothionein gene and characterization of its metal-responsive region.

The metallothionein-A gene in the metallothionein gene family of the sea urchin Strongylocentrotus purpuratus (SpMTA gene) was sequenced and found to contain three coding exons plus a 3' entirely noncoding exon. Putative alpha and beta MT domains were encoded, by its exons 2 and 3, respectively, in reverse of the order in vertebrate metallothionein genes. The SpMTA promoter was characterized through the expression of recombinant constructs containing various portions of the proximal 678-base-pair (bp) 5'-flanking region of the SpMTA gene. Zygotes injected with constructs were cultured to the blastula stage in the presence of a heavy-metal chelator and then incubated in the presence or absence of cadmium. The longest constructs were expressed only when heavy-metal ion was present. Two putative metal-responsive elements (MREs a and b) within 240 bp of the transcription start site resembled mammalian MREs in their critical 8-bp cores (TGCRCNCS) and in their locations relative to each other and to the TATA box. Elimination of activity by site-specific mutations in MREs a and b, separately or in both, identified them as metal regulatory elements. Thus, MRE recognition in this invertebrate resembles that in vertebrates. Upstream sites with single-mismatched MREs neither acted as MREs nor amplified the activity of MREs a and b. The SpMTA, Spec1, and CyIIIa actin genes, which have the same ectodermal specificity, have common DNA elements at relatively similar locations in their promoter regions; however, these elements are insufficient in themselves to promote gene expression.

Amino Acid Sequence

Limited esophagogastrectomy for carcinoma of the cardia. Indications, technique, and results.

Between 1970 and 1988, 149 patients with carcinoma of the cardia were operated on at the Lahey Clinic. Of these patients, 127 (85%) underwent resection; 23 (18.1%) were of a palliative nature. More than 75% had Stage III and IV disease. One patient (0.8%) died within 30 days of the operation of a myocardial infarct. Two other patients failed to leave the hospital. Of 25 postoperative complications, 14 (11%) were considered major. Palliation of dysphagia was successful in 80% of patients. The actuarial 5-year survival rate was 22.4%. Of patients with Stage I and II disease, 36.6% survived for 5 years, and of patients with Stage III disease, 22.5% survived. No patient with Stage IV disease lived for longer than 1 year. It is concluded that limited esophagogastrectomy can be performed in most patients with carcinoma of the cardia with low mortality and morbidity and with satisfactory long-term survival.

Adenocarcinoma

Long-term results of resection of renal cell cancer with extension into inferior vena cava.

From July 2, 1971 to April 1, 1985, 47 patients (median age 63 years) with renal cell cancer extending into the renal vein or inferior vena cava were evaluated and treated. Two-thirds of the tumors occurred in men and three-fourths were found in the right kidney. Of the 44 patients operated on 35 had no evidence of preoperative metastatic disease at operation. The patients were divided into ideal, favorable and unfavorable subgroups. The adjusted 5 and 10-year survival rates in the former 2 groups (32 patients) were 68.8 and 60.2 per cent, respectively. In contrast, 12 patients with nodal involvement or metastases had an adjusted median survival time of 1.2 years with no survival extending beyond 4.8 years. We believe that an extended operation for renal cell cancer with involvement of the vena cava is warranted and provides reasonable long-term survival in properly selected patients.

Aged

Evaluation of blood donors with elevated serum alanine aminotransferase levels.

We evaluated 100 asymptomatic blood donors with serum alanine aminotransferase (ALT) levels exceeding 0.83 mu kat/L, for evidence of liver disease or risk factors for non-A, non-B hepatitis and followed serum ALT levels for another 6 months. In 92 donors completing the study, ALT elevations occurred once in 33%, intermittently in 36%, persistently in 28%. Twenty-two donors were obese, 5 had clinical and biochemical evidence of alcoholic liver disease, and 45 drank alcohol regularly; 1 had hemochromatosis, and another, myopathy. In 22 no cause for elevated serum ALT levels was found. The presence or absence of risk of acquiring hepatitis did not correlate with the pattern of ALT elevations or the identification of another cause for the elevated ALT levels. In 92 blood donors with an initially elevated ALT level, two-thirds have intermittent or persistent elevations; most approximately 20% have no apparent cause for the elevations other than possible non-A, non-B hepatitis. These findings may be helpful in counseling and following blood donors with elevated ALT levels.

Adult

Transthoracic versus extrathoracic esophagectomy: mortality, morbidity, and long-term survival.

Extrathoracic esophagectomy for carcinoma is an acceptable substitute for transthoracic resection if it can be shown to have comparable or superior safety and no adverse effect on long-term survival. To test this hypothesis, we employed extrathoracic esophagectomy in 30 consecutive patients with carcinoma of the esophagus from January, 1978, to July, 1984. During this period, 65 comparable patients underwent transthoracic resection through a left thoracotomy for lower esophageal lesions or a right thoracotomy and laparotomy for upper thoracic lesions. Only patients with carcinoma limited to the gastric cardia were excluded from the study. Overall morbidity was higher in the extrathoracic than in the transthoracic group (13 of 30 or 43.3% versus 15 of 65 or 23.1%; p = 0.05), but the differences in hospital mortality (4 of 65 or 6.2% for the transthoracic group versus 4 of 30 or 13.3% for the extrathoracic group) and duration of hospital stay (17.4 +/- 11.7 days for the transthoracic group versus 20.5 +/- 13.4 days for the extrathoracic group) were not statistically significant. Considering all patients who either died or sustained a postoperative complication, we found significant differences favoring transthoracic resection in those subgroups of patients who were able to undergo primary reconstruction at the time of resection (12 of 57 or 21.1% versus 15 of 28 or 53.6%; p = 0.004), those with advanced Stage III lesions (11 of 47 or 23.4% versus 12 of 20 or 60%; p = 0.006), those with tumor of the lower esophagus (8 of 35 or 22.9% versus 6 of 10 or 60%; p = 0.04), and those with tumor that could be resected through a left thoracotomy (2 of 18 or 11.1% versus 17 of 30 or 56.7%; p = 0.002). Actuarial survival curves for all transthoracic and extrathoracic resections and separate analysis for Stage I and Stage III tumors revealed no statistically significant differences between these two techniques.

Aged

Segmental pancreatic autotransplantation with pancreatic ductal occlusion after near total or total pancreatic resection for chronic pancreatitis. Results at 5- to 54-month follow-up evaluation.

Reported are eight patients with idiopathic chronic pancreatitis and two patients with alcoholic pancreatitis who had near total distal pancreatectomy for disabling pain and underwent simultaneous segmental pancreatic autotransplantation of the body and tail of the gland to the femoral area in an attempt to prevent or delay the onset of diabetes. The median follow-up period was 31 months, and follow-up study in nine patients ranged from 24 to 54 months. Patency of the grafts was determined by angiography and selected percutaneous venous assays for insulin. Islet cell function was determined by oral glucose tolerance tests, intravenous (I.V.) glucose tolerance tests, and I.V. glucagon stimulation studies. Segmental autotransplantation was technically successful in eight patients, only one of whom required insulin (at 2 years after grafting). The other seven patients with technically successful grafts have remained insulin independent, including two patients who later underwent pyloric preserving pancreatoduodenectomy for completion pancreatectomy. Variable pain relief was observed in patients who underwent near total pancreatectomy, but pain was unrelieved in those patients who underwent limited distal resection. Patients with idiopathic pancreatitis appear to have better pain relief and preservation of endocrine function than alcoholic patients. Segmental pancreatic autotransplantation prevents or delays the onset of diabetes mellitus and should be considered as an alternative for those patients who require extensive pancreatic resection for chronic pancreatitis.

Adult

Pyloric and gastric preserving pancreatic resection. Experience with 87 patients.

Eighty-seven patients with neoplasm (57 cases), pancreatitis (28 cases), or benign biliary obstruction (2 cases) were treated with pyloric preserving pancreatectomy with two postoperative deaths, neither due to abdominal complications. About 50% of patients had delay in recovery of gastrointestinal function. Six and seven patients had clinically significant biliary and pancreatic fistulas, respectively, with some patients having both. Complications required 16 reoperations. Marginal ulcer was suggested by endoscopy or barium study in five patients, three of whom were successfully managed by a medical regimen. In the other two patients, exploration failed to demonstrate an ulcer or jejunitis. In most patients, long-term gastrointestinal function was judged to be excellent based on weight gain and lack of digestive symptoms. Pyloric function and gastric motility were evaluated by abdominal scanning using indium 111 and technetium 99m. Gastric emptying of liquids and solids was normal. Estimations of enterogastric reflux showed a moderate difference between normal subjects and pancreatectomy patients. Cancer-free survival was comparable to that after the standard Whipple procedure.

Adenocarcinoma

Vascularized versus nonvascularized nerve grafts: an experimental structural comparison.

This study compared the success of nerve regeneration through conventional nonvascularized and vascularized nerve grafts in the sciatic nerve of rats. The number or size of regenerated axons between the two grafts was not significantly different. In addition, the ratio of axonal diameter to total diameter of the nerve, a measurement linearly related to conduction velocity, was not significantly different in the two groups. Thicker myelin sheaths were found around axons in the nonvascularized nerve grafts.

Animals

Target-specific nerve regeneration through a nerve guide in the rat.

Nerve regeneration across a gap in peripheral nerve has been achieved through various nonneural nerve guides in both lower and primate species. This technique can only be useful if the regenerated nerve cable grows specifically to and reinnervates the appropriate distal target. In this study, the proximal peroneal fascicle of rat sciatic nerve was inserted into the proximal limb of a Y-shaped nerve guide. Distal peroneal and tibial fascicles were placed within the two distal limbs of the same Y. The proximal peroneal nerve grew preferentially by a 2:1 ratio to the appropriate distal peroneal fascicle suggesting that target-specific reinnervation is possible through a nerve guide.

Animals