Gastrin antibodies: induction, demonstration, and specificity.

Antibodies to the antral hormone gastrin have been induced in the rabbit and detected by passive hemagglutination. Specificity of the antibody, as determined by three methods, is directed to gastrins I and II, gastrin pentapeptide, and gastrin tetrapeptide, as well as to the stage-1 gastrin used for immunization.

The distribution of the glycosaminoglycans in the anatomic components of the lung and the changes in concentration of these macromolecules during development and aging.

The glycosaminoglycans of the normal human and bovine lungs and of the major structural components of these organs (pleura, 'alveoli', peripheral and central bronchi, arteries and veins) were investigated. To carry out this study, a micromethod for the separation and quantitative determination of these macromolecules, namely two-dimensional electrophoresis on cellulose acetate plates, was employed. This procedure made it possible to measure the content of each glycosaminoglycan present in the mentioned anatomic components. In the human lung the distribution of the glycosaminoglycans varies considerably from one component to another: dermatan sulfate was the predominant mucopolysaccharide of the pleura, chondroitin 6-sulfate that of the central bronchi, and heparan sulfate and chondroitin sulfate those of the alveoli. Heparin and keratan sulfate were not detected in any of the structural components. Significant changes in the mucopolysaccharide levels were found during maturation and aging. Further age-related changes were noted between 22 and 39 years. In the bovine lung significant changes in the glycosaminoglycan levels were also observed during growth and aging. Heparin appeared in the lung at an age between 1 and 16 months. Similarities and differences in the total contents and compositions of the glycosaminoglycans between the human and bovine lung were noted.

Pharmacokinetics of epoetin (recombinant human erythropoietin) after long term therapy in patients undergoing haemodialysis and haemofiltration.

After long term therapy with epoetin (recombinant human erythropoietin) 17 patients with end-stage renal disease (ESRD) were studied in 3 groups to assess pharmacokinetics during the intertreatment interval and during haemofiltration and dialysis treatment. Epoetin was measured by radioimmunoassay. After an intravenous bolus of epoetin 150 U/kg bodyweight, the half-life was 7.7h, steady-state volume of distribution was 0.066 L/kg and total plasma clearance was 5.4 ml/min. The mean steady-state serum concentration during multiple-dose administration was 656 U/L. The drug was not eliminated by haemofiltration or dialysis. Long term treatment of ESRD patients with epoetin does not significantly alter the pharmacokinetic profile of the drug. Epoetin dosage adjustment or substitution after haemofiltration and dialysis is not necessary.

Gastrinoma: factors influencing prognosis.

The gastrinoma remains the only endocrine-producing pancreatic tumor for which early surgical intervention is not uniformly advised. It should be possible after 30 years to determine the factors that appear to influence survival. Forty patients who underwent surgery 10 years or more ago were reviewed in an effort to identify factors at operation and the type of surgical procedure that influence survival. Because the total number of patients is small, conclusions based on statistics are not justified; however, certain trends have become clear. Favorable factors at surgery were the presence of a verified submucosal duodenal tumor, the presence of multiple endocrine neoplasia, or the failure to find tumor. Unfavorable factors were the presence of liver and/or lymph node metastases and/or a verified sporadic, nonfamilial pancreatic tumor. Thirty-four of the 40 patients underwent total gastrectomy, and 18 of these patients also underwent hemipancreatectomy, while six underwent other procedures less than total gastrectomy. The 10-year survival rate was 50%. The long-term quality of life in surviving patients who underwent total gastrectomy supports the original recommendation of total gastrectomy.

Mechanisms of oxygen free radical-induced calcium overload in endothelial cells.

Unregulated increases in intracellular calcium levels with subsequent cytoskeletal disruption have been implicated in tissue injury caused by oxygen free radicals (OFRs). The purpose of these experiments was to study the kinetics of free intracellular calcium in endothelial cells on exposure to exogenous OFRs and investigate the mechanisms of this altered homeostasis. Monolayers of endothelial cells were labeled with a calcium-sensitive probe and exposed to exogenous OFRs generated with hypoxanthine and xanthine oxidase. Intracellular calcium changes were monitored dynamically by continuous measurement of fluorescence with a spectrofluorometer. A sustained rise in intracellular Ca++ levels reaching a peak at 5 minutes was observed. This effect was blocked by superoxide dismutase and catalase. Removal of calcium from the medium or chelating the extracellular calcium with ethyleneglycoldiamine tetraacetate significantly blunted the response to OFRs (p less than 0.05). Preincubation of the cells with verapamil did not alter the observed increase in Ca++i. Addition of another divalent cation (Mn++) to the medium partially blocked the rise in calcium levels (p less than 0.05). Membrane potential measurements assessed fluorometrically, with the fluorescent probe bisoxonol, demonstrate a transient hyperpolarization of the plasma membrane on exposure to OFRs, temporally associated with the rise in [Ca++]i. In summary, OFRs cause an increase of intracellular calcium in endothelial cells. This response is dependent on extracellular calcium and independent of voltage-sensitive calcium channels. The increase can be partially inhibited by other divalent cations. These results suggest that the transformation of the plasma membrane components (lipid peroxidation and cross-linking of proteins) caused by OFRs may produce cation ionophores.

Breast biopsy for calcifications in nonpalpable breast lesions. A prospective study.

We prospectively studied 239 consecutive patients who underwent breast biopsy for 277 nonpalpable lesions characterized by mammographic microcalcifications. Clinical and mammographic characteristics were correlated with histologic findings in an attempt to identify patients more likely to have early breast cancer. The distribution of clinical risk factors was equal between patients with benign or malignant outcomes. The predominant Wolfe pattern on mammography was P2 (38%); however, no relationship was observed between the Wolfe pattern and malignancy. A marked correlation was observed between malignancy and small lesions, more than 15 calcifications, and calcifications in a linear or branching pattern. Twenty-four percent (n = 67) of the biopsy specimens contained either ductal or lobular breast cancer. This study highlights the necessity of an aggressive approach toward suspicious calcifications found by mammography.

Primary tumor size. Relevance to breast cancer survival.

In view of current emphasis on identifying prognostic factors for patients with early breast cancer, we studied the importance of tumor size to survival among 1392 patients with primary operable breast cancer who were followed up prospectively. All patients had modified radical mastectomies. Nine hundred seventeen patients had negative nodes and did not receive postoperative adjuvant therapy. Four hundred seventy-five patients had node involvement and received combination chemoendocrine therapy. In a Cox's proportional hazards model, tumor size was a significant predictor of disease-free and overall survival when the number of positive nodes, estrogen receptor status, menopausal status, and race were considered. Among the node-negative group, tumor size explained considerable variation in disease-free and overall survival, varying from a 10-year disease-free and overall survival of 80% and 99% for patients with estrogen receptor-positive tumors measuring 1 cm or less to a 10-year disease-free and overall survival of 51% and 59% for patients with tumors larger than 5 cm.

Not all nonpalpable breast cancers are alike.

Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease.

Age does not predict breast cancer outcome.

OBJECTIVE: To determine whether age is a prognostic factor of breast cancer and should be used to make treatment recommendations, because younger patients are considered to have a poorer prognosis compared with that of older patients and, thus, often receive more aggressive therapy. DESIGN: A large group of patients with operable breast cancer, all of whom were followed up prospectively as part of two multicenter trials. SETTING: Case Western Reserve University, Cleveland, Ohio, was the primary hospital and study center, with 12 participating regional institutions. PATIENTS: All 1353 patients underwent uniform local-regional therapy that consisted of a modified radical mastectomy. Patients who were node negative were followed up, and patients who were node positive received systemic chemoendocrine therapy. MAIN OUTCOME MEASURES: Patients were followed up at regular intervals for either recurrence or death. RESULTS: Patients ranged in age from 22 to 75 years with a median age of 56 years. Younger patients had more estrogen receptor-negative tumors (P < .0001) and a greater number of positive lymph nodes (P < .0001). Of the 241 black patients in the study, a greater percentage were younger compared with white patients (P < .0001). Age was considered in a Cox's multivariate model, together with nodes, tumor diameter, estrogen receptor content, and race. Age was not a significant predictor of either disease-free (P = .33) or overall (P = .30) survival. Using mixture models with covariates, the estimated average hazards (where lambda indicates the force of mortality) of breast cancer deaths per year were similar (P, not significant) for patients 45 years old or younger (lambda = 0.061), older than 45 years but 65 years old or younger (lambda = 0.052), and older than 65 years (lambda = 0.061). CONCLUSIONS: In conclusion, younger patients as a group have more aggressive and advanced breast cancer at presentation compared with older patients. Considered in a multivariate model, together with other variables, age does not provide independent prognostic information and should not be used alone for management decisions.

Simplified technique for the surgical palliation of pulmonary atresia with right ventricular hypoplasia and intact septum.

A rapid, simple palliative technique for treatment of pulmonary atresia with a one-stage pulmonary valvotomy and central aortopulmonary artery shunt is described.

Islet cell tumors of the pancreas and the alimentary tract.

Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely.

Primary neoplasms of the small intestine.

Over a 20 year period, 64 patients with primary neoplasms of the small intestine were treated by celiotomy (61 patients) or surgical endoscopy (3 patients). Gastrointestinal bleeding and anemia (38 percent of patients) characterized benign lesions, whereas pain (42 percent), nausea and vomiting (26 percent), weight loss (29 percent), and either gastrointestinal obstruction or jaundice (18 percent) were more indicative of malignancy. Barium studies, duodenal endoscopy, and selective angiography were the most useful diagnostic tools. All 26 patients with benign lesions did well after resection, whereas the 38 patients with malignancies did poorly despite apparently curative wide excision in 19 and pancreaticoduodenectomy in 6. Only the patients with malignant carcinoid lesions treated surgically and by chemotherapy had a good 5 year survival rate (60 percent). All patients with sarcomas and adenocarcinomas died from their disease. Major operations and chemotherapy gave fair outcomes in only a minority of patients who had no evidence of metastasis. These results document the need to suspect small intestinal neoplasms earlier and to perform more aggressive diagnostic workups in patients with vague gastrointestinal symptoms.

Critical analysis of jejunoileal bypass.

This study analyzed a group of morbidly obese patients who underwent jejunoileal bypass over a 10 year period. Patients underwent either a Payne or Scott procedure. Weight loss was reported in terms of percent of excessive weight loss. Results showed that patients who had a Payne bypass had an average excess weight loss of 75 percent, whereas those with the Scott bypass had an average excess weight loss of 61 percent. All patients lost weight. Complications in this series were lower than what has been traditionally reported. The problem that occurred most often was kidney stones (8 percent of the patients). There has been only one death to date. The low incidence of complications can be attributed to the fact that the patients were evaluated, operated on, supervised, and followed by one doctor and his associated nurses. Thus, it is proposed that jejunoileal bypass, compounded with good patient care and careful patient selection, can produce positive results with a minimum number of problems.

Role of surgery in antibiotic-induced pseudomembranous enterocolitis.

With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease.

Pitfalls in ambulatory treatment of inguinal hernias in adults.

Careful patient selection and preparation for ambulatory inguinal herniorrhaphy combined with monitored local anesthesia result in a safe procedure with excellent patient acceptance. Factors contributing to early and late complications are presented, and the common methods of their treatment are reviewed.

Metastatic malignant biliary obstruction.

Jaundice due to metastatic tumor involving the extra-hepatic bile ducts is uncommon, and thus, the management of this problem is not standardized. Retrospective analysis of all patients admitted to University Hospitals of Cleveland with malignant biliary obstruction was thus undertaken to identify the incidence, origin, management, and outcome of these metastatic tumors. During a 5-year period, 56 patients with jaundice secondary to biliary, pancreatic, ampullary, or metastatic tumors were identified. Of these, 12 (21%) represented a distant malignant process metastatic to the porta hepatis. Sites of origin were diverse: lymphoma, 2; breast, 3; colon, 2; and 1 each with Hodgkin's, lung, ovary endometrium, and melanoma. Patients ranged in age from 31 to 90 years (mean: 60). Surgical intervention was undertaken in only two patients (cholecystojejunostomy, 1; transhepatic U-tube stenting, 1). The remainder were managed as follows: no procedure, 3 (25%); percutaneous stenting, 5 (42%); and radiation only, 2 (17%). Mortality was as follows: 5 of 12 (42%) died within 30 days and 8 of 12 (67%) within 60 days. The only survivors beyond 60 days were the patients with Hodgkin's (1 of 1), lymphoma (1 of 2), breast (1 of 3) and melanoma (1 of 1). Ten of the patients had obvious extensive metastatic disease, which would explain the poor outcome. Analysis of this data indicates that overall survival is dismal and palliative, nonoperative methods to manage the jaundice should be considered.

Radiographic measurements of alveolar bone loss in the rat.

A new method to evaluate alveolar bone loss in rodents is described. The palatal and lingual halves of maxillae and mandibles were radiographed. On enlarged positive prints, 5 vertical distances were drawn at defined sites from the cemento-enamel junction to points revealing fully intact bone structure. These were either located on the alveolar crest or at the depth of intrabony defects. These distances were recorded with a trace-reading pen coupled to a computer. Results were expressed in mm for each site separately and totals (left plus right values) for either maxillae or mandibles were calculated. This technique was compared to other methods for evaluating alveolar bone loss, using the jaws of rats subjected to a gnotobiotic regime in which the degree of bone loss was low. It was demonstrated that the measurement of vertical distances based on radiography by which also intrabony defects were defined was accurate, reproducible and more sensitive than other means of evaluating bone loss.

Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis.

A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery.

Intrapulmonary foreign body: sponge retained for 43 years.

We present a patient who had a left thoracotomy 43 years previously. Since that surgery he experienced intermittent hemoptysis, and a recent thoracotomy revealed an intrapulmonary foreign body (retained sponge) in the left lower lobe. The liability potential of this case is discussed.

The spectrum of appendiceal disease in cystic fibrosis.

A retrospective review of 1,220 cystic fibrosis (CF) patients between 1965 and 1989 identified 60 patients who underwent appendectomy. Ten had appendectomy prior to referral and 16 had an incidental appendectomy (primarily meconium ileus). Among the remaining 34 patients, acute appendicitis was present in 19 (1.8% incidence). "Classic appendicitis"--acute abdominal pain shifting to the right lower quadrant (RLQ), focal RLQ tenderness, and elevated white blood cell (WBC) count--was present in 15. Four additional inflamed appendixes were removed in patients following incorrect preoperative diagnosis. Thirteen of these 19 were perforated. Complications included wound infection (2), pelvic abscess (1), ileal obstruction requiring ileostomy (1), and pelvic hematoma (1). There were no deaths. One patient with acute RLQ pain and tenderness had a normal appendix. Seven patients (mean, 20 years) had chronic, intermittent, focal RLQ pain and tenderness not originating periumbilically with a normal WBC count and temperature. At exploration, these appendixes were enlarged and tensely distended with inspissated mucus. Microscopic examination showed no inflammation. Appendectomy resulted in resolution of symptoms without complications. Four additional patients with intermittent RLQ pain and tenderness and a history of recurrent intussusception presented with ileocolic intussusception. Persistent postreduction symptoms in three and failure of reduction in the fourth necessitated celiotomy at which time tensely distended appendixes were removed. Appendectomy led to resolution of symptoms. Three additional enlarged noninflammed appendixes were incidentally removed in asymptomatic patients undergoing unrelated intraabdominal procedures. Appendiceal disease in CF patients represents a spectrum ranging from simple mucous distention to acute appendicitis with perforation. CF patients with pain secondary to a noninflamed distended appendix represent a distinct syndrome cured by appendectomy.(ABSTRACT TRUNCATED AT 250 WORDS)