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Biomedical subjects

R H Bell

Publications and source records attributed to R H Bell.

At least 55 records · Page 3Linked to original sources

Inhibitory effect of streptozotocin on tumor development in transgenic mice bearing an elastase I-SV40 T-antigen fusion gene.

Transgenic mice, bearing a fusion gene of rat elastase I promoter and SV40 T-antigen, developed acinar cell tumors of the pancreas, as predicted by the model. In addition, they developed insulinomas and somatostatin (delta)-cell hyperplasia of the pancreatic islets. The insulinomas and the delta-cell hyperplasia appeared to be functional, as evidenced by changes in plasma glucose, insulin, and somatostatin. Streptozotocin, which has been shown to inhibit pancreatic carcinogenesis in the hamster model, significantly reduced the numbers of insulinomas and delta-cell hyperplasias. Streptozotocin did not cause a statistically significant reduction in exocrine tumors.

Animals↗

An appreciation of posterior instability of the shoulder.

Fortunately, posterior instability of the shoulder is a relatively uncommon occurrence in the athlete. Acute traumatic posterior dislocations can be readily managed by conservative measures. Recurrent posterior subluxation, however, represents a more challenging problem for the orthopedic surgeon. As has been discussed, most patients with this disorder respond to nonsurgical treatment including physical therapy and modification of the offending activities. Should these modalities fail, operative treatment may be necessary. Careful assessment of the patient to rule out the associated presence of excessive ligamentous laxity or a voluntary component to the instability is mandatory. Pain is clearly the principal indicator for surgical treatment. Painless subluxation, either voluntary or involuntary, should first be treated conservatively. The surgical options discussed in this article range from simple soft-tissue repair to more complex osteotomies with combined capsular plication. It is important that the procedure be appropriate to the pathology. We do not believe that one technique alone can address all variants of posterior instability. Most instances of recurrent posterior subluxation represent unidirectional instability in patients with otherwise normal bony morphology. In these patients, a posterior capsulorrhaphy combined with appropriate immobilization should be effective. In select instances, when either excessive glenoid retroversion or deficiency is encountered, a glenoid osteotomy and posterior capsulorrhaphy have proved successful. This technique, more than any other, carries a number of potential technical pitfalls and should be employed cautiously. Multidirectional posterior instability, now a well-recognized entity, requires a different surgical approach--the capsular shift. Designed to address the inferior redundancy, as well as posterior laxity, this procedure is applicable to the multidirectional posterior subluxator. In conclusion, posterior instability of the athlete's shoulder is an increasingly recognized entity. Most instances are amenable to nonsurgical care. Should surgical treatment be necessary, optimal results may be achieved by careful attention to patient assessment, instability categorization, determination of the presence of ligamentous laxity, and appropriate surgical technique.

Humans↗

Full-thickness rotator-cuff tear. An analysis of results.

A retrospective review is reported on 68 patients with 72 full-thickness rotator-cuff tears treated surgically. Duration of symptoms before surgery averaged 18 months (range, one month to ten years). Tears of the rotator cuff were divided into small (12 shoulders), medium (26 shoulders), large (17 shoulders), and massive (17 shoulders). Rotator-cuff tears were repaired by use of a bony trough in 88% of patients. All patients were treated with decompression acromioplasty. In addition, an acromioclavicular arthroplasty was performed in 29 patients. Forty-seven men and 21 women with an average age of 58 years (range, 31-76 years) were followed for an average of 24 months (range, nine to 57 months). Excellent results are reported in 46 shoulders, good in 20, fair in four, and poor in two. The size of tear and duration of symptoms did not significantly affect results.

Adult↗

Further studies of enhanced growth of pancreatic carcinoma in diabetes.

Clinical studies suggest that pancreatic cancer occurs more often in persons with diabetes mellitus [1-7]. We have previously shown that the hamster pancreatic carcinoma cell line H2T grows more rapidly when implanted in streptozotocin (STZ)-diabetic hamsters [8]. To determine if enhanced growth of pancreatic carcinoma cells in diabetic hamsters is due to polyphagia associated with diabetes, H2T cells were implanted into the cheek pouch of three groups of animals: normal hamsters (group I), STZ-diabetic hamsters (group II), and STZ-diabetics pairfed to normals (group III). Tumor weights 30 days after implantation were 172 g in group I, 368 g in group II, and 369 g in group III (P less than 0.007). There was no significant difference between the two diabetic groups. Thus, STZ diabetes appears to promote the growth of pancreatic carcinoma cells by a mechanism other than increased nutrient intake by diabetic tumor hosts.

Animals↗

Study of surgical resident working hours and time utilization.

Recently, changes have been suggested in resident working hours and conditions. Few objective data exist, however, as to how many hours surgical residents work or how they utilize their time. Surgical residents on four every-third-night general surgery services (two services in the University Hospital and two in the Veterans Hospital) kept a log of their activities divided into 15-min intervals 24 hr a day for 4 weeks. Activity for each 15-min interval was entered into one of nine predesignated categories. Residents spent an average of 95.8 hr per week in the hospital, working 85.8 hr and sleeping 10 hr. Overall, residents slept an average of 5.9 hr per night, 4.2 hr on on-call nights and 6.2 hr on off-call nights. Operating and direct patient care activities consumed 8.7 hr per day (10.25 hr Monday to Friday). Patient care activities which residents believed could be performed by nonphysicians accounted for 1.5 hr per day. An average of 1.8 hr per day was spent in conferences or independent study. This survey provided objective data regarding working hours and time utilization for our residency. Both residents and faculty found that time spent in various activities differed from preconceived notions. We suggest that program directors may find a formal survey of this type useful in assessing the structure of their own residency and in providing objective data to compare to or determine compliance with externally generated guidelines.

General Surgery↗

Neuropeptide Y and peptide YY stimulate the growth of exocrine pancreatic carcinoma cells.

Neuropeptides exert inhibitory effects on pancreatic secretion, but their role in the regulation of growth is unknown. This study was executed to evaluate the effects of PYY and NPY on cell growth and 3H-thymidine incorporation in human (MiaPaCa-2, Capan-2) and hamster (H2T) exocrine pancreatic carcinoma cells in vitro. A significant increase in the number of cells after 96 h of treatment with NPY was observed at 0.01 microM in H2T, 0.1 microM in MiaPCa-2 and at 1 microM in Capan-2 cells. PYY was less potent and did not increase significantly cell growth in MiaPaCa-2, but did at 0.1 microM in Capan-2 and at 1 microM concentration in H2T. Stimulation for 48h with NPY increased 3H-thymidine incorporation significantly at 0.01 microM in all cell lines. With PYY, stimulation of 3H-thymidine incorporation occurred in H2T cells at 0.01 microM. 3H-thymidine incorporation after PYY treatment was significantly increased at 0.1 microM in MiaPaCa-2 and at 1 microM in Capan-2 cells. Receptor studies showed low but definite specific binding of both NPY and PYY in all cell lines. The results suggest that NPY and PYY may have a role in the regulation of growth of exocrine pancreatic carcinoma cells.

Adenocarcinoma↗

Hyperplasia and tumors of the islets of Langerhans in mice bearing an elastase I-SV40 T-antigen fusion gene.

Transgenic mice bearing a fusion gene consisting of rat elastase I 5' flanking DNA fused to the early-coding (T-antigen) region of the SV40 genome (ELSV mice) develop carcinomas of the acinar cells of the exocrine pancreas. Histopathological examination of pancreatic tissue from 79 such animals revealed that, in addition to acinar cell neoplasms, ELSV mice develop two distinct lesions of the islets of Langerhans. By the age of 26 weeks, 36% of the mice had developed insulinomas. Starting at 8 weeks of age, the mice also developed D (somatostatin)-cell hyperplasia, which began at the periphery of the islets but which in advanced cases resulted in nearly complete replacement of other islet cell types by D-cells. By 26 weeks of age, 85% of the mice examined demonstrated the D-cell abnormality. Both the insulinomas and D-cell lesions were negative by immunohistochemistry for T-antigen, which was, however, demonstrated in acinar cell neoplasms using a monoclonal antibody against a C-terminal T-antigen epitope. Insulinomas have been described in other SV40 transgenic mice, particularly when the SV40 enhancer is not included in the transgene, suggesting that the presence of native SV40 enhancer may ordinarily suppress the expression of T-antigen in pancreatic beta-cells. The somatostatin-cell lesion is unique to the ELSV model; it may be neoplastic or represent a response to the growth and neoplastic changes occurring simultaneously in the exocrine pancreas.

Adenoma, Islet Cell↗

Alteration of pancreatic endocrine cell patterns and their secretion during pancreatic carcinogenesis in the hamster model.

Proliferation of endocrine cells was found to occur during early, i.e., first 12 weeks, exocrine pancreatic carcinogenesis after 6 weekly treatments of Syrian hamsters with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Cells containing insulin (Ins), glucagon (Glu), and somatostatin (Som) were noted in all stages of tumor development and were present in adenocarcinomas and in metastases to the liver. Some of the cancer cells were of amphicrine (hybrid) type, i.e., produced both mucin and endocrine substances. Measurement of these hormones revealed a significant decrease in plasma Ins during early stages of carcinogenesis with concomitant increase of Ins level in pancreatic juice at 12 weeks after 6 weekly BOP treatments. Plasma Glu and Som were not changed. The changes noted, particularly in relation to Ins, suggest that proliferation of endocrine cells in pancreatic carcinogenesis may be associated with alterations in hormone secretion.

Animals↗

Importance of diabetes in inhibition of pancreatic cancer by streptozotocin.

Previous studies in our laboratory have demonstrated that the beta-cell toxin streptozotocin (STZ) inhibits the development of exocrine pancreatic cancer in the hamster when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Because the administration of STZ leads to diabetes, we wished to determine whether the presence of diabetes was important in the inhibitory effect of STZ on pancreatic carcinogenesis or whether STZ acted through a mechanism unrelated to diabetes, perhaps by a direct toxic effect on tumor precursor cells. Whole pancreas transplantation was used to create a two-pancreas hamster model to test this hypothesis. The study demonstrated that (1) STZ inhibits the induction of pancreatic cancer in the hamster when given prior to BOP and (2) the inhibitory effect of STZ was demonstrable only when diabetes was present. The inhibitory effect of STZ appears to be systemic, related to diabetes, and not a direct effect on the pancreas.

Animals↗

Total shoulder arthroplasty.

Seventy Neer Series II total shoulder arthroplasties were performed in 65 patients. The average age was 69 years. The average follow-up period was 40 months. Rheumatoid arthritis or osteoarthritis was the diagnosis in 34 and 29 shoulders, respectively. Rotator cuff tears were identified in 18 patients. There were no infections, neurological injuries, or vascular injuries, or vascular injuries. Two glenoid fractures and two humeral shaft fractures were sustained intraoperatively. Uniformly, excellent pain relief was obtained regardless of the disease process. The resultant average increase in range of motion (ROM) was 60 degrees of active forward elevation and 18 degree of external rotation. Radiolucent lines were present in 17 humeral components; however, none was symptomatic or had progressed in thickness. Five glenoid components demonstrated progression of radiolucency, and two required revision. Both of these were in patients with rheumatoid arthritis. Although pain relief was uniformly good among all patient groups, a statistically significant degree of improvement in ROM was found in individuals with osteoarthritis. The etiology of the disease process and the status of the rotator cuff may determine the eventual outcome in individuals treated with total shoulder arthroplasty.

Adult↗

Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma.

Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of 125I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.

Adenocarcinoma↗

Influence of diabetes on susceptibility to experimental pancreatic cancer.

Clinical studies suggest that diabetes mellitus may predispose to the development of pancreatic cancer. The current study investigated the effect of experimental diabetes on the susceptibility of the Syrian hamster to the induction of exocrine pancreatic carcinoma by the carcinogen BOP. Diabetes was induced with the B-cell toxin streptozotocin. Three groups of animals were studied: nondiabetic control animals and animals with streptozotocin-induced diabetes, and a third group of animals in which the diabetogenic effect of streptozotocin was blocked with nicotinamide. Streptozotocin-induced diabetes significantly inhibited the induction of pancreatic carcinoma by BOP, decreasing the incidence of carcinoma to 24 percent compared with an incidence of 75 percent in nondiabetic control animals (p less than 0.002). In diabetic animals, the degree of inhibition of carcinogenesis paralleled the severity of the diabetes. Blocking the diabetogenic effect of streptozotocin with nicotinamide restored the incidence of induced invasive pancreatic carcinoma to that occurring in nondiabetic control animals. In the hamster model, diabetes appears to have a strong influence on susceptibility to the development of pancreatic carcinoma.

Animals↗

Evaluation of developmental toxicity data: a discussion of some pertinent factors and a proposal.

There is currently no well-accepted standard method for evaluation of developmental toxicity data. This paper presents one approach to the evaluation of developmental toxicity data. We initially identify some pertinent factors that influence the interpretation of animal data and summarize the literature pertaining to these factors. Such factors include the quality and quantity of data and the relationship between maternal and developmental toxicity. We proceed with a discussion of quantitative assessment of data and propose schemes for qualitative and quantitative developmental hazard assessments.

Animals↗

Comparison of seven plating media for enumeration of Listeria spp.

The suitability of seven media for the enumeration of Listeria spp. was evaluated at 30 degrees C for 48 h. The media tested were (i) the original McBride Listeria agar formulation (with glycine); (ii) modified McBride agar containing glycine anhydride; (iii) LiCl-phenylethanol-moxalactam (LPM) agar; (iv) acriflavine-ceftazidime agar; (v) Rodriguez isolation agar (RISA); (vi) modified Vogel-Johnson (MVJ) agar; (vii) cyclohexanedione-nalidixic acid-phenylethanol agar; and tryptose agar as control. A total of 66 organisms were used including 11 Listeria monocytogenes strains and 5 other Listeria spp. For L. monocytogenes strains only, all media performed highly similarly. Of the other Listeria spp., only two grew on MVJ agar and three each grew on LPM and RISA. Only LPM agar inhibited the 50 non-listeriae, including five yeasts, while MVJ agar inhibited all but one yeast. The McBride Listeria agar formulation that contained glycine anhydride was less selective than the original. When pure cultures of 10 bacteria (including one L. monocytogenes strain) were combined and plated on four media, L. monocytogenes colonies were easiest to enumerate on MVJ agar, followed by LPM and RISA. These media ranked in the same order when plated with homogenates of various foods to which was added L. monocytogenes Scott A, but LPM agar was the best overall since Scott A was inhibited by MVJ. Upon microscopic examination of listerial colonies from the plating media, atypical cell morphology was noted with cells being about twofold in size on LPM, MVJ, and acriflavine-ceftazidime agars. Overall, LPM agar was the most suitable of the media tested even though it was inhibitory to Listeria grayi and Listeria murrayi.

Colony Count, Microbial↗

Diabetes enhances growth of pancreatic carcinoma cells.

Clinical studies suggest that carcinoma of the pancreas may be more common in patients with chronic diabetes mellitus. To examine the effect of diabetes on growth of pancreatic carcinoma, 5 X 10(5) cultured hamster H2T pancreatic carcinoma cells were implanted into the cheek pouches of streptozocin-diabetic and nondiabetic Syrian hamsters. Tumor size and weight and total tumor DNA content 22 days after implantation were significantly greater in animals with diabetes. Thus streptozocin diabetes appears to promote the growth of pancreatic carcinoma cells in the hamster.

Adenocarcinoma↗

Carcinoid tumor of the biliary system. Case report and literature review.

Work-up of a 62-year-old black male, with a complaint of low back pain for three months, revealed a mass in the porta hepatis, narrowing of the common hepatic duct, and dilated intrahepatic bile ducts. A 3 X 4-cm tumor in the common hepatic duct was excised and biliary continuity restored by hepaticojejunostomy. The excised mass was a carcinoid tumor with no evidence of secretory activity. The patient is well 24.5 months after treatment. The literature on carcinoid tumors of the biliary tract is reviewed.

Bile Duct Neoplasms↗